Throughout the game, the puppies have to rescue their siblings, fend off Cruella's henchmen, and Cruella herself several times, while navigating through all kinds of terrain, leading up to a final battle at Cruella's Toy Factory, during which Cruella (and her "Dot Com Darling," Dr. Farzboom) are encased in Farzboom's own creation, "supergloop."
Over the course of the game, you have several opportunities to collect "stickers" towards a virtual sticker book which can be accessed through the level menu. Various actions within the game will unlock stickers. Generally, there's a sticker for finding the first checkpoint and exiting every level, collecting 100 bones each level, and rescuing all the puppies in each level. Each level has its own individual tasks - completing a chore, defeating a henchmen, solving a puzzle, etc. - which will also grant stickers. There are six stickers per a level, excluding Cruella levels, which combine together with Minigames for their own sticker image.
Puppies to the Rescue is a 3-dimensional game with the ability to angle the camera in whichever direction will make it easiest for you to navigate. Necessary, too, unless you like being dive-bombed by random toy planes from behind. The game contains a few minor glitches, like walls which jumping over cause you to drop at the starting point on the level, but these are harmless and don't damage your progress. You must bark at toys to short-circuit them, our roll into them to smash them.
Checkpoints within a level are places where you will be sent back if you lose a life, and are marked by a parrot named Waddlesworth. If you lose a life and have not reached a checkpoint, you will be sent back to the level's starting point. Unlike the Game Boy Color version of the game, toys you fry stay broken.
Each level has an "animal friend" who will tell you how to get through the level, and sometimes assign you specific tasks to do in return for their help. Completing each of the Cruella levels will unlock a minigame to play.