The show revolves around the adventures of three girls with superpowers: Blossom, Bubbles, and Buttercup. They were created by Professor Utonium in an attempt to create the “perfect little girl” using a mixture of “sugar, spice, and everything nice.” However, he accidentally spilled a mysterious substance called “Chemical X” (In the pilot it was a Can of Whoopass) into the mixture, creating, instead of the “perfect little girl”, three girls with amazing powers.

The plot of an episode is usually some humorous variation of standard superhero and tokusatsu shows, with the girls using their powers to defend their town from villains and giantmonsters.

In addition, the girls have to deal with the normal issues that young children face, such as sibling rivalries, loose teeth, personal hygiene, going to school, bed wetting, or dependence on a security blanket.

Episodes often contain hidden references to older pop culture (especially noticeable in the episode “Meet the Beat Alls,” which is an homage to the Beatles). The cartoon always tries to keep different ideas within each episode with some small tributes and parodies thrown in.