A 56-day feeding trial was conducted to evaluate the dietary effect of Nigeria polyherbal mixture (PHB) on growth, haemato-immune parameters, antioxidant enzyme activities, and intestinal morphometry of African catfish, Clarias gariepinus. Four diets were formulated with PHB powder at inclusion of 0 g/kg (control), 0.5 g/kg (PHB 0.5), 1.0 g/kg (PHB 1.0), and 2.0 g/kg (PHB 2.0) and fed to African catfish (
6.32
±
0.02
g
/fish, 15 fish/50 L tank) in triplicates. Fish fed PHB 2.0 recorded higher final weight, weight gain, and specific growth rate (
p
<
0.05
) compared to the control. There were no statistical differences (
p
>
0.05
) in feed conversion ratio and protein efficiency ratio among the dietary groups. The haematological profile indicates that the fish fed PHB-1.0 had higher Hb, RBCs count, and Hct, and blood performance (
p
<
0.05
) compared to the control. ALT levels were found higher in the control and the lowest values recorded in PHB groups (
p
<
0.05
); however, AST did not differ significantly among the groups (
p
>
0.05
). The highest heterophil counts and respiratory burst activity were recorded in PHB-1.0 and PHB-0.5 and PHB-2.0, respectively, while a numerically improved total immunoglobulin value was recorded in PHB-0.5 compared to the control (
p
>
0.05
). Antioxidant enzymes such as superoxide dismutase and catalase had a significant improvement in fish fed PHB-based diet compared to the control (
p
<
0.05
), while glutathione peroxidase showed no statistical differences between the groups (
p
>
0.05
). Intestinal morphometric measurements showed that the fish fed PHB-1.0 had the highest villus height, area of absorption, and villus height/cryptal depth ratio compared to the control. Muscle thickness increased (
p
<
0.05
) with increasing PHB level with the highest value recorded PHB-2.0. In conclusion, dietary PHB could improve growth, blood profile, immunity, antioxidant enzyme capacity, and intestinal morphometry of African catfish without any significant alteration in the liver function enzymes.