Gargamel has kidnapped Smurfette. As a Smurf, the player has to walk from the Smurf village through a forest and a cave on the way to Gargamel's castle, where Smurfette awaits rescue. The player has an energy bar that slowly depletes over time.
Each side-scrolling screen presents various obstacles that the player must precisely jump over (e.g. fences, stalagmites) or land upon (e.g. ledges). Failure to execute any jump results in instant death. Higher difficulty levels introduce flying bats and spiders that the player must also avoid.
The ColecoVision version of Smurf: Rescue in Gargamel's Castle contains an Easter egg. Upon reaching Smurfette's screen, the player can return to the previous screen. Just before the screen changes, it will appear as though the top of Smurfette's dress comes off, making her appear topless.