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- Clifford as Numbuh 1 (their signature color is red)
- Mac as Numbuh 2 (their signature color is blue)
- Mimi as Numbuh 3
- T-Bone as Numbuh 4
- Cleo as Numbuh 5 (Cleo & Numbuh 5 are voiced by Cree Summer)
- Kiki as Laura Limpin (Numbuh 5's little sister)
- Emily Elizabeth as Numbuh 362
- Ben Diskin - Mac and Clifford
- Lauren Tom - Mimi
- Dee Bradley Baker - T-Bone
- Cree Summer - Cleo
- Grey DeLise - Kiki
- Rachel MacFarlane - Emily Elizabeth