Five isonitrogenous and isolipidic diets (Diet 1–Diet 5, with Diet 1 as the control) were formulated to replace 0%, 20%, 40%, 60%, and 80% of fishmeal with American cockroach residue. Juvenile Cyprinus carpio (initial body weight approximately 74 g) were randomly assigned to these diets for a 10-week feeding trial. The Diet 3 group (40% replacement) showed significantly higher final body weight, weight gain rate, specific growth rate, and protein efficiency ratio compared to other groups. No significant differences were observed in crude protein, ash, and total amino acid content across the diets. Groups fed Diet 1 and Diet 2 exhibited higher intestinal trypsin, lipase, α-amylase, and hepatic trypsin activities. Serum triglyceride (TG) levels were highest in the Diet 5 group. Hepatic aspartate aminotransferase (AST) activity was significantly lower in the Diet 3 and Diet 5 groups compared to Diet 1. Serum urea nitrogen levels followed a non-linear trend, initially increasing, then decreasing, and rising again with increasing fishmeal replacement. No significant differences were found in serum total protein (TP) levels among the dietary groups. Intestinal villus number, muscle layer thickness, villus height, villus width, and crypt depth remained consistent across groups. However, goblet cell numbers were significantly reduced at the 60% replacement level, which could impair intestinal barrier function. Diet 3 showed higher serum and hepatic total superoxide dismutase (T-SOD) activity, while Diet 2 had the highest hepatic total antioxidant capacity (T-AOC) activity. Hepatic malondialdehyde (MDA) levels were lowest in the Diet 2 and Diet 5 groups. Immunoglobulin M (IgM) levels showed an increasing trend with higher fishmeal replacement levels. In conclusion, replacing fishmeal with American cockroach residue did not adversely affect growth performance or body composition in juvenile C. carpio. Substituting 20–40% of fishmeal with American cockroach residue enhanced antioxidant capacity and immune function in juvenile C. carpio.
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