- Seto Kaiba provides much of the games humour, as he has a tendency to insult most characters and laugh a lot.Kaiba: So the merry band of losers finally have a clue about what's really going on.
- The Duelist Computer's assessment that Tristan and Duke are both idiots.
- Any time Yugi, Joey, or Kaiba summon their signature monsters and have them destroyed as they call their attacks. It's even funnier if the Blue-Eyes White Dragon is destroyed by Kuriboh, thanks to its element.
- Jean Claude Magnum tries to marry Mai again, dueling the player for her hand in marriage. Mai warns you that you better not lose.
- Everyone thinking Reshef's magic somehow turned Tristan into a robot monkey, then deciding that the one who's lousy at dueling must be him.
- If you go back to Italy before the Neo Ghouls invade, you'll run into Jean-Claude Magnum again, who hears from Bonz that if he can beat three duelists in a row he'll be able to marry Mai. When the player defeats him, Magnum decides to go challenge weak duelists, only for Bonz to say after he runs off that if he loses even once his fortune changes.
- Bonz's fortune-telling. He says that in a previous life, the player character was a Duel Monster. Which one it is is based on your name. He also reads into your romantic life and your future if you talk to him repeatedly, and one of your future opponents can be a stray dog.
- The Mimic of Doom's impersonation of Yami Yugi is offset by him saying "dude" and insisting that his disguise is perfect.
- Mako Tsunami's reason for refusing to duel Strings.Mako: Can you do something about this person? I lack the skill to deal with such weirdness.
- When dueling Bandit Keith, he can and will tribute three monsters to summon the Winged Dragon of Ra... in Sphere Mode. A Divine Monster with 0 Attack and Defense. This is even funnier if beforehand, his monsters had been defeating you.
- Due to looping sprite animations, Para and Dox can backflip up flights of stairs.
- Joey mistakes Paradox's name for Parachute, prompting Yugi to correct him.
- By entering a certain password at the shop, you can change the appearance of the final boss. It's Goemon Impact! Even funnier is that the dialogue doesn't change.
Funny / Yu-Gi-Oh! Reshef of Destruction