Matthew Broderick
John Brown / Inspector Gadget / Robo Gadget

Rupert Everett
Sanford Scolex / Dr. Claw

Joely Fisher
Brenda / Robobrenda

Michelle Trachtenberg
Penny

Andy Dick
Kramer

Cheri Oteri
Mayor Wilson

Mike Hagerty
Sikes

Dabney Coleman
Chief Quimby

D.L. Hughley
Gadgetmobile (voice)

René Auberjonois
Artemus Bradford

Frances Bay
Thelma

Laurence Tureaud
Himself

Richard Kiel
Famous Big Guy with Silver Teeth

Richard Lee-Sung
Famous Villain with Deadly Hat

Bobby Bell
Famous Identifier of Sea Planes

Hank Barrera
Famous Native American Sidekick

Keith Morrison
Famous Assistant to Dr. Frankensomething

John Kim
Son Before Second Son

Cliff Emmich
Out of Control Bus Driver

Richard Penn
Fantastic Doctor