- Michael York as Sherlock Holmes
- Malcolm McDowell as Professor James Moriarty
- John Rhys-Davies as Doctor Watson
- Grey DeLisle as Red, parody to Irene Adler
- Jeff Bergman as Butch the Bulldog, Droopy
- Phil LaMarr as Spike, Policeman
- Greg Ellis as Tin, Sergeant
- Jess Harnell as Pam, Brett Jeremy
- Richard McGonagle as Ali, First Policeman
- Kath Soucie as Tuffy
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