- Why is the show so deliberately ugly? Two reasons: one, puberty makes you feel ugly, so it wouldn't make sense for pubescent children to look anything other than gangly and awkward. Two, it dissuades any assumptions that it's an excuse to draw naked pubescent children, because who would find these kids attractive?
- The Shame Wizard's shame inducement has NO effect on Coach Steve, because he is so childlike and unabashed, meaning he simply doesn't have any shame.
- Nick's character design is a homage to a certain joke:Why do most men like women with big boobs and tight pussies?
Because most men have big mouths and small dicks.
- Hormone Monsters often makes suggestions about sex and intimacy that makes no sense, like Maurice telling Matthew to kiss a boy by mashing his teeth against his. However, this makes an interesting amount of sense when you consider them to represent the kid's subconscious: they make suggestions that make no sense because the kids also aren't really clear about how sex and sex acts work.
- Jay's superhero moniker being "Cum-Bender" has a secondary meaning: "bender" is a slur against people of the LGBT+ persuasion.
- It may seem odd for Andrew to suddenly have a masturbation method in "Four Stories about Hand Stuff" when he hasn't before, but it could have developed as a coping mechanism since almost every other masturbation or ejaculation he's had in the show has led to something bad happening to him (the dance with Missy, the bathroom with Leah, etc.).
- In the ending of season 4, both Tito and Depression Kitty shrunk down to the size of normal mosquitos and cats respectively after Jessi manages to help Nick out and figure out her own problems, but they did not disappear. Why? It's a metaphor that while you cannot completely remove anxiety and depression, you can manage them in healthy ways.
- When Matthew comes out to his dad, he looks like he's getting irritated by where the conversation is going, but then it's revealed that he already knew Matthew was gay and never had a problem with it. He was just annoyed that they changed the subject from a topic that he found interesting to something he thought was a mundane non-issue.
- Probably unintentional, in the Queer Eye episode, one of the Fab Five describes Coach Steve as Clark Gable meet Super Mario. Coach Steve's full name is Steve Steve like Super Mario's is Mario Mario.
- Hate Worms acquire a serpent-like appearence the more they're allowed to fester. While this could just be to make them more intimidating, wurms or wyrms are also a type of dragon.
- At first, I always thought it was a bit of a misaimed message that the show talked about puberty when it was very clearly an adult-only show. But after thinking about it, I realized it's not for kids to learn about puberty; its so parents and adults can understand what children are going through so that they can better help them through those issues. In other words, it's a guidebook for future parents or carers.
- But it's still incredibly popular with kids going through puberty as well. This just goes to show that Big Mouth, like most legendary cartoons, was created to be a show that can resonate with two audience demographics, kids and adults.
- "Rice Purity Test" implies that Jay committed bestiality. Assuming the beast in question doesn't have to be alive, it's probably referring to that incident with the Thanksgiving turkey.
- Again in "Rice Purity Test", since Jay considers giving a handjob to a close friend on top of a water tower after taking dog dewormers to be committing incest, joining the mile-high club, and using horse tranquilizers/meth/crack/heroin/pcp, it's likely his score of 3 is because he's being incredibly liberal with his definitions.
- Crossing with Genius Bonus, the Rice Purity Test anthropomorphized as a cowgirl with a country line dance song is a reference to the test's origins from Rice University, a private college in Houston, Texas.
- The writers deserve praise for making lovebugs and hateworms the same entity. They could have gone the easy route and made them two different species that fight all the time but making them the same is a brilliant metaphor for how love and hate are both identical feelings that come from the same place.
- Several characters, such as Lars and the Gogurt Burglar, disappear between seasons 3 and 4. They have two classmates who are established to be cannibals...
- Lars and Gogurt burglar both show up during season 5 so safe to say at least those two weren't eaten.