Pokémon Puzzle Challenge (ポケモンでパネポン, Pokemon de Panepon), is a video game for the Game Boy Color. It was based on the game Panel de Pon, only with characters from the Pokémon franchise. The characters in Pokémon Puzzle Challenge were based on those in the Gold and Silver games, while those in Pokémon Puzzle League—its Nintendo 64 equivalent—were based more on the anime characters. However, the game is also focused around beating the Johto leaders in a puzzle challenge in Johto region. The game play mode is divided into 1 Player, 2 Player, and Training.

Pokémon Puzzle Challenge features Pokémon characters in a version of Panel de Pon, known as Tetris Attack in North America. Panel de Pon featured unique characters for both player-characters and opponents; similarly, Pokémon such as Pikachu, Pichu, Cyndaquil, Totodile, and Chikorita appear as playable heroes, while Gym Leaders, trainers, and the Elite Four from Pokémon Gold and Silver appear as opponents, all of them utilizing a single Pokémon used in Gold and Silver. It features the ability to collect Pokémon by battling trainers in order to unlock new Pokémon to play as. Similarly, the music in the game was taken from Gold and Silver. Players attempt to meet a goal, achieve a high score, or outlast opponents by preventing blocks from reaching the top of the player's playingfield. The game has three modes of play — single player, multi player, and training modes. There are also several other sub-modes: Marathon, Challenge, Time Zone, LineClear, Puzzle, and Garbage!.

Marathon involves playing infinitely until players lose; Challenge is a versus computer or another player, involving forming combos to force the opposition to lose, though unlike other versions of the game, only the player's puzzle is visible, the opponent's replaced with a meter indicating how close they are to losing; Time Zone involves forming a high enough score in a certain amount of time; LineClear involves clearing levels by reaching a certain number of lines; Puzzle involves clearing a select number of blocks in a certain number of turns; and Garbage! is similarly to Marathon in being infinite, except garbage blocks fall on players' field, making it more difficult. With the exception of Puzzle, reaching the top in any of these modes results in the mode ending. The gameplay is largely the same as in other games in the Puzzle League series; players control a two square long cursor that can swap or move blocks around the field. The objective is to clear blocks in at least three block clears or more; players are encouraged to "combo" these clears by having that one clear lead to another clear. In certain modes, comboing clears will cause objects called garbage blocks to fall on enemies' areas with intent of forcing them to reach the top, thereby ending the round in players' favour. Unlike its counterparts on other platforms, it uses a smaller puzzle grid.