- Clash of the Titans: The game's title is a pun on this movie's name.
- The Wizard of Oz: The game is packed with references to this book:
   - "The Blizzard of Claws" is a pun on the book's title.
   - "The Emerald Pity" is a pun on The Emerald City, which is a recurrent place in the books of this series.
   - "Don't Eat the Yellow Brick Load" is a reference to the line "Follow the yellow brick road.".
   - After defeated, some Doom Monkeys say "I'm melting! I'm melting! Oh, what a world, what a world!", which is what the Wicked Witch of the West says upon melting.
- Star Wars Episode IV: The title of the first episode of the game is a pun on the fourth episode of Star Wars (A New Hope). Additionally, Uka Uka at one point says "A tremor in the Mojo! The last time I felt it was in the presence of my older brother, Aku Aku.", which is a reference to one of Darth Vader's lines in this movie ("A tremor in the Force. The last time I felt it, was in the presence of my old master.")
- Leroy Jenkins: Sometimes a Doom Monkey will scream "LEEEEEROOOOYYY!!" while charging at Crash, a reference to the famous World of Warcraft player and Internet phenomenon, Leroy Jenkins, who yelled out his name as he charged into enemy territory, after completely missing his colleagues' extensive plan, causing all of their characters to die.
- Invader Zim: N. Gin sometimes sings the Doom Song, which originated in the animated show Invader Zim.
- The Simpsons: After defeated, some Doom Monkeys say "Two more will take my place!", which was first said by an executive in The Simpsons. Doom Monkeys also sometimes say "D'oh!", Homer Simpson's famous line of frustration.
- The Doors: Doom Monkeys sometimes say "This is the end..." after defeated, which might refer to the lyrics of a song from The Doors, entitled The End.
- Gremlins (movie): The Voodoo Bunnies' description parodies Gizmo from the movie Gremlins, a creature who shouldn't be wet or fed after midnight, in order not to multiply into multiple evil 'mogwai'.
- Nirvana: One of the Mojo Rooms is named "Smells Like Green Spirits", a reference to a song from Nirvana called Smells Like Teen Spirit.
- Planet of the Apes: Crash complaining and throwing a tantrum at N. Gin's statue (which is a parody of the Statue of Liberty) parodies the end of the original Planet of the Apes movie, in which Taylor curses upon discovering the Statue of Liberty.
- Super Mario: Ratnicians sometimes say "You'd think he was an Italian plumber or something.", a reference to Super Mario.
- Sonic the Hedgehog: Ratnicians sometimes say "You'd think he was a fast-moving hedgehog or something.", referring to Sonic the Hedgehog.
- Minority Report: The episode "Minority Rapport" is a pun on this movie's title.
- Moonraker: The "Doomraker" episode's name is a pun on this James Bond novel/movie.
- Flubber: Some Ratnicians say "He's like Flubber, the mystery stuff!", a reference to the 'flubber' substance in the eponymous film.
- Braveheart: Voodoo Bunnies often yell "FREEDOM!", a famous line in the movie Braveheart, said by William Wallace.
- Lost in Space: After defeated, Ratnicians sometimes say "Danger, Will Robinson!", one of the Robot's most repeated lines in the show Lost in Space.
- Star Trek II: The Wrath of Khan: Ratnicians sometimes scream "KHAAAAN!!", just like Captain James Kirk in this movie.
- Indiana Jones and the Temple of Doom: Episode 4, "The Temple of Zoom", is a pun on this movie's title.
- Pop Idol: N. Gin sometimes says "I could be on Cyborg Idol, if that show existed.", a reference to the show Pop Idol and its many international spin-offs.
- The Matrix: Doom Monkeys sometimes say "There is no spoon.", like the spoon kid in The Matrix.
- MySpace: One Brat Girl says to another that she should film herself defeating Crash and put the video on MySpace.
- Deliverance: Koo-alas, the hillbillies in this game, sometimes say "You've got a purty mouth, boy.", similar to what one of the hillbillies in this movie says.
- Mortal Kombat: Doom Monkeys sometimes say "FINISH HIM!", the famous finish-off line in the Mortal Kombat games. They also sometimes say "Mortal Kombat!".
- SpongeBob SquarePants: Some Ratnicians say "Barnacles!" when defeated, which is one of SpongeBob's lines.
- The Lord of the Rings: The scene with N. Gin talking to himself as if he were two different people (including the camera angle changes) is a parody of Golem from The Lord of the Rings, who does the same thing in the movie.
- The War of the Worlds: The episode title "War of the Whirls" is a pun on this novel/movie's name.
- A Bridge Too Far: The episode named "A Sludge too Far" is a pun on this book/movie.
- Shock and Awe: Episode 11, "Shock and Awesome", is a pun on this military code.
- Amityville Horror: The episode "Calamity Ville Horror" is a pun on this book's title.
- Scarface: The GBA version has Cortex saying "Say hello to my little friend!", a line from the movie Scarface. The console versions sport a parody of the Scarface mansion in "War of the Whirls", complete with a statue of Cortex holding the World.
- Operation Overlord: The episode "Operation Overboard" is a pun of Operation Overlord, the Allies' plan to storm France via beaches and parachute drops and liberate it from the Axis Forces.
- Liberace: Cortex playing a piano with a candelabrum on it is a reference to Wladziu Valentino Liberace, who as an American pianist. A second reference occurs when N.Gin says "I wish my brother George was here", just like Liberace would do in reference to his older brother, who happened to be his business partner.