Pokémon Puzzle Challenge is a puzzle-based game in Generation II created for the Game Boy Color where the player must play puzzle games. The gameplay of this game is similar to Tetris Attack and Pokémon Puzzle League. In Challenge Mode, the player starts out with the three Pokémon, Totodile, Cyndaquil, and Chikorita. This game has a multiplayer feature.
- Marathon - This mode is an endless mini-game on where the player must gain as much points as possible until the entire screen gets filled up with blocks. There is an Easy, Medium, and Hard mode.
- Challenge - The player controls Gold in this game on where he must battle Johto Gym Leaders who send out garbage occasionally. This has an Easy, Medium, and Hard mode too. The final opponent on the Easy mode is Clair, medium mode is Karen, and on hard mode is Lance.
- Time Zone - The player must gain as much points as possible in two minutes.
- Line Clear - The player must play through six rounds and five stages and a bonus stage and encounter various Johto Gym Leaders.
- Puzzles - The player must clear the blocks in until his/her moves run out.
- Garbage - This mode is the same as Marathon, but with two changes: Garbage Blocks fall down randomly from the sky and the scroll speed does not change.
- Falkner's Pidgey
- Bugsy's Kakuna
- Whitney's Clefairy
- Morty's Gastly
- Chuck's Primeape
- Jasmine's Steelix
- Pryce's Seel
- Clair's Dragonair
- Will's Jynx
- Koga's Crobat
- Bruno's Hitmontop
- Karen's Murkrow
- Lance's Dragonite
Pikachu is the only non-Generation II introduced playable Pokémon and character.