An 84-day feeding trial was performed to investigate the effects of dietary curcumin (CUR) supplementation on growth performance, feed utilization, immunity, antioxidant response, and resistance to Aeromonas hydrophila in Oreochromis niloticus. Three hundred tilapia fish (average initial weight; 2.55 ± 0.003 g) were fed five diets supplemented with 0 (basal diet), 50, 100, 150 or 200 mg CUR kg− 1 diet. Herein, a concentration-dependent inhibition of both A. hydrophila and A. sobria following in vitro CUR treatment was evident. The in vivo results revealed that CUR supplementation at different levels, especially at 50 mg kg− 1 diet, evoked significantly higher final weight, daily weight gain, and specific growth rate in tilapia. Also, CUR100 and CUR150 fish groups had the best feed conversion and protein efficiency ratios. Also, a significant increase in both crude lipid and protein content of the whole body was recorded in fish fed 50 or 100 mg CUR kg− 1 diet. A significant increase of both catalase activity and reduced glutathione content with a significant incline in the MDA level were recorded with dietary CUR supplementation. Lysozyme activity, total IgG and IgM levels significantly increased, especially in fish fed the 50 mg CUR kg− 1 diet. A concentration-dependent decline in the total bacteria, Coliforms, Escherichia coli and Aeromonas spp. counts was recorded in water samples and intestinal content of tilapia with CUR addition. High survival rate was obvious in all CUR supplemented groups after challenge with A. hydrophila. It is concluded that CUR could be a candidate dietary supplement in fish improving growth performance, feed utilization, oxidative status, immune responses, and disease resistance.