Background: This study was carried out to assess the performance indices, nutrient digestibility, and carcass trait of weaner rabbits fed diets containing cassava peel meal (CPM) supplemented with methionine (MET) and multi-enzyme (ENZ). Two hundred and forty 5-week-old growing rabbits were randomly allotted to 8 dietary treatments (10 replicates/treatment) in a factorial arrangement (2 × 2 × 2) of 2 CPM inclusion levels (0 and 35%), 2 MET levels (0.56 and 0.83%), and 2 ENZ levels (0 and 0.05%). Results: The final weight gain (1563.16 g), daily weight gain (17.67 g), and feed conversion ratio of rabbits fed diet 5 (35% CPM; 0.56% MET) were significantly (P < 0.05) lower than those fed the rest of the diets. While the 35% CPM dietary inclusion significantly led to the performance and dry matter digestibility reduction, the high methionine (0.83%) and multi-enzyme (0.05%) significantly (P < 0.05) improved the final weight gain (FWG) and feed and conversion ratio in the rabbits. The interactive effect of methionine and multi-enzyme supplementation on FWG of the rabbits was significant (P < 0.05). Dry matter (DM) digestibility decreased (P < 0.05) with CPM inclusion, while the DM, organic matter (OM), crude protein (CP), acid detergent fiber, and gross energy (GE) digestibility improved (P < 0.05) with high methionine (0.83%) and enzyme supplementation. The slaughter weight (SLW), carcass weight, and carcass weight percentage of rabbits on diet containing 35% CPM and 0.56% methionine but without enzyme supplementation (diet 5) was significantly (P < 0.05) lower than the rest of the diets. There were significant (P < 0.05) increases in liver and kidney weights of rabbits fed diet 5. Conclusion: The growing rabbit's diet with 35% CPM inclusion will require the supplementation of methionine at a high level in addition to multi-enzyme supplementation to achieve a desired performance by the farmer.