Curcumin, a polyphenol, targets multiple signaling molecules and shows activity at the cellular level, supporting its various health benefits. Thereafter, the present study examines the effects of different doses of dietary curcumin on growth indices, feed efficiency, serum metabolites, redox (oxidation) status, immunity, histological assessment, and antioxidant-related genes in red tilapia (Oreochromis sp, Oreochromis aureus x O. mossambicus). A total of 1200 red tilapia with an average weight of 19.1±0.03 g were distributed in 12 cement ponds (3×3.5×1m). Each treatment was assigned three pounds (n=100 replicates). For 60 days, fish were fed baseline diets containing 0, 0.4, 0.6, and 0.8 g of curcumin/kg of diet. The treated fish showed increased body weight and SGR (specific growth rate) compared to the T0 group (P<0.05). Curcumin in the diet significantly improved weight gain, percentages, and FCR (feed conversion ratio), with a dose-dependent effect (P < 0.05). Curcumin supplementation showed no influence on feed intake, fish mortality, or survival rate (P >0.05). The curcumin-treated fish groups improved tissue structure in hepatocytes, pancreatic lumens, hepatic blood sinusoids, and intestine tissue layers, particularly the mucosal layer. The T0.8 group had reduced liver enzymes (AST and ALT) and greater total protein and albumin levels (P<0.05). The T0.6 and T0.8 groups showed significantly lower MDA levels than the other groups (P < 0.05). Curcumin groups demonstrated significantly higher antioxidant indices (CAT, GPx, and SOD) compared to the basal diet (P<0.05). Curcumin administration resulted in significant improvements in IgM and lysosome levels (P<0.05). All supplemented groups had considerably (P<0.05) higher levels of SOD, CAT, and GPx mRNA than the control group. Consequently, administering 0.6–0.8 g/kg of curcumin to red tilapia (Oreochromis sp.) diets may improve the fish’s growth, health, tissue composition, and antioxidant response.