The impact of dietary fenugreek (FN) supplementation on growth performance, physio‐metabolic enzyme response, and antioxidant enzyme activities in hybrid African catfish (Clarias gariepinus ♀ × Heterobranchus bidorsalis ♂) was investigated in this study. Five isonitrogenous diets (38% crude protein) were developed and fed to the fish for 60 days. The FN was incorporated into the diets at 0%, 0.5%, 1.0%, 1.5%, and 2%. Two hundred twenty‐five fingerlings of hybrid African catfish (average weight 4.01 g ± 0.02) were used for the study and randomly distributed to five dietary groups in triplicate. FN supplementation improved growth responses and survival rates; the dietary groups considerably (p < 0.05) outperformed the control group. FN‐based diets considerably increased the carcass protein content (p = 0.020) and improved protein retention (p = 0.015). FN supplementation markedly (p < 0.001) and dose‐dependently reduced the carcass’s lipid content and substantially (p < 0.001) increased the levels of metabolic enzymes. The fish antioxidant capacity was significantly enhanced (p < 0.001), and hepatic stress enzymes were greatly (p < 0.001) lowered in FN‐based diets. In summary, the second‐order polynomial regression analysis indicates that the optimal dose of FN supplementation to improve hybrid catfish growth without negatively affecting the fish’s physio‐metabolic response or overall wellbeing is 1% dietary inclusion level.