Nathan Lane as Spot Helperman / Scott Leadready II / Scott Manly-Manning (voice)

Kelsey Grammer as Dr. Ivan Krank (voice)

Shaun Fleming as Leonard Amadeus Helperman (voice)

Debra Jo Rupp as Mrs. Mary Lou Moira Angela Darling Helperman (voice)

David Ogden Stiers as Mr. Jolly (voice)

Jerry Stiller as Pretty Boy (voice)

Paul Reubens as Dennis (voice)

Megan Mullally as Adele (voice)

Wallace Shawn as Principal Crosby Strickler (voice)

Rob Paulsen as Ian Wazselewski (voice)

Jay Thomas as Barry Anger (voice)

Estelle Harris as Mrs. Boogin (voice)

Genie Francis as Marsha / Marcia (voice)

Anthony Geary as John / Juan (voice)

Rosalyn Landor as The Blue Fairy (voice)

David Maples as Beefeater (voice)

Pamela Adlon as Trevor / Taylor / Tyler (voice)

Timothy Stack as Father (voice)

Emma Steinkellner as Little Girl (voice)

Ken Swofford as Officer White (voice)

Lauren Tom as Younghee (voice)

Mae Whitman as Leslie Dunkling (voice)

Kevin Michael Richardson as Conductor (voice)