The game centers on a team of superheroes who protect a futuristic metropolis from Dr. Mayhem and his robotic henchmen. The Defenders are:
Ms. Megawatt (voiced by Whoopi Goldberg in the animated series), who can shoot electric bolts
Jet Headstrong (voiced by Pat Fraley in the animated series) , who can fire his head like a rocket
Buzzsaw Girl (voiced by Candi Milo in the animated series), who has a buzzsaw blade instead of legs
Toolbox (voiced by David Coburn in the animated series), a robot with a smashing hammer head
Monkey Kid (voiced by Brian Stokes Mitchell in the animated series), a blue monkey armed with exploding bananas
Radium Dog, who can fly and has jaws strong enough to pick up cars with his mouth