Anime & Manga
- In Danganronpa 3: Future Arc, one of the paintings found in a room is one of The Mona Lisa with MonoKuma's face on it. Which makes it "The Mono Kuma".
- In JoJo's Bizarre Adventure: Diamond is Unbreakable, Yoshikage Kira tells a paramedic that he discovered his hand fetish via getting turned on by a picture of the Mona Lisa in an art book.
- A Batman Elseworlds story juxtaposed Batman investigating the theft of the Mona Lisa while on loan to the Gotham Art Museum with Leonardo's apprentice Tomas de Medici donning a bat costume designed by his master to rescue Lisa del Giocondo herself.
- In Mr. Peabody & Sherman, Peabody visits his good friend Leonardo as he is painting the Mona Lisa, struggling to get his model to smile.
- In The Bad Guys (2022), Mr. Shark's greatest crime is stealing the Mona Lisa while disguised AS the Mona Lisa.
- In Horton Hears a Who! (2008), while the Mayor shows his son Jojo a hallway of his family's ancestors he presents his "great-grandmother" who is depicted as the Mona Lisa.
- It briefly appears in Bernard and the Genie when Bernard wishes that it was hanging on the wall in his flat. Unfortunately, this causes it to disappear from the Louvre, sparking an international criminal investigation that leads right to Bernard's flat.
- Equilibrium: Mona Lisa appears as one of the paintings getting burned in the beginning of the film.
- Mona Lisa appears at the start of Hudson Hawk, being painted by Leonardo. It's revealed that the reason for the famous Mona Lisa Smile is that the subject of the painting had bad teeth.
- In the 2011 French film L'Apparition de la Joconde (The Appearance of the Gioconda), a divorced Parisian screenwriter is visited by a strange woman named Lisa who pretends to come out of the painting itself. The two of them visit the Louvre to see the painting at one point.
- In Popstar: Never Stop Never Stopping one of Conner4Real's singles for his new album is "Mona Lisa
", a song about how disappointed he was when seeing the painting for himself at the Louvre. He calls it "an overrated piece of shit", and that she "looks like a Garbage Pail Kid". - Glass Onion features the Mona Lisa as a Chekhov's Gun; eccentric billionaire Miles Bron has been noted as saying that he wants to be mentioned in the same breath as the Mona Lisa in future for creating something truly immortal, and has even essentially rented the painting from the Louvre as the museum is closed during the current COVID-19 Pandemic and France needs the money. Ultimately, Miles gets his wish when the painting is destroyed as a result of his supposedly clean energy source starting a fire that burns down his house.
- The Da Vinci Code has the painting on its most common book covers (and only its eyes on most of them).
- Early Riser takes place in an Alternate History where humans hibernate during winter, with many Different World, Different Movies examples showing how humans deal with that lifestyle. Two extant versions of the Mona Lisa are discussed, with one noted to be thin and sickly while a second is said to look plump and healthy as she gorges herself in preparation for winter.
- The Way Things Work: The page explaining how earphones work shows the Mona Lisa wearing them.
- The 1979 Doctor Who serial "City of Death" features a villain who is attempting to steal the Mona Lisa, having previously gotten Leonardo to paint him six more back in 1505 so that he can steal the "original" in 1979 and sell all seven to private collectors for a hundred million dollars to finance his real Evil Plan.
- In The Good Doctor episode "Zero Point Three Percent", Dr. Glassman says during brain surgery, "Look at that. That's what built the pyramids, painted the Mona Lisa, invented the internet."
- Monty Python's Flying Circus: In the "Art Gallery Strike" sketch, portraits in various paintings go on strike, including the Mona Lisa, who puts on a cap, says, "I'm off," and walks out of the painting.
- In the first season finale of Sherlock Holmes, "The Final Problem" has Professor Moriarty concoct a plot to steal it and privately sell fakes to collectors under the pretense that they're the real painting. After Holmes foils his scheme, Moriarty starts actively targeting Holmes leading to their final clash at the Reichenbach Falls.
- The 2005 My Hero episode "Nothing to Hide" has the superhero Thermoman, alias George Sunday, taking the Mona Lisa home with him after confiscating it from an art thief. Before he can return the painting, it is punched through the face by his angry father in-law, who had assumed it to be a fake. To avert disaster, Thermoman picks up the still living, actually an alien, 500+ year old Leonardo da Vinci from his home planet to paint the Mona Lisa again, which he obliges after first painting a Blue Period version, believing his original to be "old cliched crap". As a superpowered Ultronian, da Vinci is able to whip up a new Mona Lisa in a matter of seconds.
- The Murdoch Mysteries episode "Murdoch and the Mona Lisa" is set in the aftermath of the 1911 robbery, with Perrugia briefly visiting Toronto and being embroiled in (but not responsible for) a murder relating to copies being sold as the original. The painting is correctly portrayed as well known to art lovers like Inspector Brakenreid, but not the popular cultural touchstone it became afterwards. Also, the real one possibly ended up in the Brakenreids' house in the belief it was one of the fakes.
Music
- David Byrne: The choruses of "The Call of the Wild" ask "What made Mona Lisa smile?"
- One frequently-covered song since the 1950s is simply entitled "Mona Lisa", written by Ray Evans and Jay Livingston for the Paramount Pictures film Captain Carey USA (1950). The song itself is a straightforward ode to the mystique both of the painting and the subject Lisa Gherardini. Nat King Cole's cover version is likely the most recognizable and still used in popular culture—to the extent that even documentaries about the painting are likely to use it.
- Queen: In the Title Track to The Miracle, the painting's perpetual smile is contrasted with the hostilities of the Cold War, with Freddie Mercury describing this apparent perseverance of optimism as one of the many miracles that the song lists.
- In Safe Havens it's hinted that the true identity of Mona Lisa is Candide Fuerte, when Leonardo promises to come back to what for him is the future when they're older to paint her, and she's seen in Mona Lisa's pose.
- The Mona Lisa appears in the Animal Crossing series as an acquirable painting that you could either put up in your home, or donate to the museum. Its in-game title is called the “famous painting”.
- In the DLC "The da Vinci Disappearance" of Assassin's Creed: Brotherhood, the unfinished painting can be seen in a cutscene where Ezio Auditore visits Leonardo at his workshop in Rome, circa 1506. Ezio thinks Leonardo is doing a "decent work" on it, and Leonardo is much more critical of his own work, thinking she is "badly drawn" and that her smile is "overdone and meaningless".
- One level in Elite Beat Agents has the Agents help Leonardo win the heart of a beautiful but emotionless young women. Clearing the level will have the woman give off a beautiful smile, which in turn inspires Leonardo to draw the painting based on her.
- Mona Lisa herself is a playable character in the mobile RPG Grimms Notes Repage.
- In Fate/Grand Order, Leonardo chose to model themselves after the Mona Lisa, stating that the Mona Lisa was the ideal in beauty to strive for. Leo once even claimed Mona Lisa was their gender. (It should be noted that this is a notable departure from other Gender Flips in this series, as most of them are a case of 'really the opposite gender in real life', Leonardo chose to present as a female.)
- In No Umbrellas Allowed, one of your customers sells you the Mona Lisa, and the original one at that since the Year Estimator confirms that it was made in 1503.
- In Potion Permit, the Mona Lisa can be found in Hannah's and Nova's bedrooms and on the 1st floor (2nd floor in American English) of the town hall.
- Rayman: The loading screen for Picture City has Rayman making a recreation of the painting, albeit with himself in the role of the Mona Lisa.
- Terraria: a version with the Nurse in the role of the Mona Lisa can potentially be found as a painting in an underground cabin.
- Mona Lisa's Silly Talk has Mona Lisa mentioned right in the title, and the title screen has mascot characters, Mona and Lisa, shown in Mona Lisa-esque portraits.
- Looney Tunes: The Pepé Le Pew cartoon "Louvre Come Back to Me" ends with Pepe in the air vents of the Louvre, his smell affecting all the paintings; Mona Lisa's reaction, however is more subdued, deadpanning the line on the stinger on the main page.
- Pinky and the Brain: In Issue #3 of the comics, Brain's attempts to pass himself off as a woman include The Mona Lisa.
- Name-dropped in an episode of The Venture Brothers when Phantom Limb is trying to sell Rembrandt's Storm On The Sea Of Galilee, but the Nouveau Riche mafiosi says he wants the Mona Lisa. Phantom Limb responds that he can't get it, and that the only reason that painting is famous is because it was stolen, as is the one he currently has (it was stolen from a Boston museum in 1990 and has yet to be recovered).
- In the Courage the Cowardly Dog episode "So in Louvre Are We Two", two planets aligning causes all the paintings and sculptures of the Louvre to come to life. Mona Lisa is among them, and spends the night trying to win the affections of The Thinker, and quickly gets exasperated with his indecisiveness. She ends up running off with the male half of Rodin's The Kiss while the Thinker ends up stuck in the painting Nighthawks, still trying to decide what to eat.
- Madeline: The episode "Madeline at the Louvre" has Miss Clavel naturally takes the girls to see the Mona Lisa. Chloe and Nicole get into a brief argument on whether she's actually smiling or not.
- In the Ready Jet Go! episode "The Mindysphere", Sunspot shows a drawing on his tablet of Mindy posing like the Mona Lisa. He calls it the "Mindy Lisa".
