New antioxidants as antibiotic substitutes are urgently required in aquaculture as their liver protection and anti-inflammatory effects. To explore the potential value of American cockroach (Periplaneta americana) powder water extract (ACPWE) as an antioxidant substitute for genetically improved farmed tilapia (GIFT, Oreochromis niloticus), different concentrations of ACPWE were added to the GIFT feed and its effects on growth performance, foregut histologic morphology, and some biochemical indices were measured. ACPWE had no significant effect on GIFT weight gain, feed conversion, specific growth rates, or condition factors. The viscerosomatic index of GIFT exposed to ACPWE was lower, indicating that ACPWE reduced the GIFT visceral mass. ACPWE had no significant effect on the length and width of foregut villi.At ACPWE concentrations >1.5 g/kg, serum aspartate aminotransferase (AST) and alanine aminotransferase, and liver AST concentrations decreased, whereas serum and liver total protein concentrations, catalase, total superoxide dismutase, and glutathione peroxidase activities, and total antioxidant capacity increased. Based on the observed serum and liver biochemical and antioxidant indices, adding 1.5 g/kg ACPWE to feed could improve GIFT antioxidant ability.