A 56-day feeding trial was performed to determine the effect of replacing fishmeal with 0, 25%, 50%, 75%, and 100% PBM (FM) on growth performance, digestive enzyme, and immunity of juvenile giant river prawn (Macrobrachium rosenbergii). Diets were fed in quadruplicate (50 prawns per replicate) to satiation (3–5% of their body weight). The finial weight, weight gain, and specific growth rate of prawns were significantly reduced P < 0.05 when 100% PBM was substituted for fish meal, whereas the remaining test diets showed no variation compared to the control P > 0.05 . There was no significant difference in survival rates. The moisture, crude protein, and crude fat of the prawn were unchanged P > 0.05 . The SOD activity, MDA content, and AKP activity of hemolymph did not change significantly. However, the ACP activity of all replacement groups decreased significantly P < 0.05 . The amylase enzyme activity in the intestine of prawn fed 25% of PBM increased significantly compared with the control group, while the trypsin and lipase activities were unchanged. This study showed that PBM up to 75% replacement group does not affect growth performance, and all replacement groups have no adverse effect on intestinal digestive enzyme activity and immunity in juvenile M. rosenbergii. Therefore, poultry by-product meal could replace fish meal by up to 75%.