The study aims to investigate the potential effect of nanocurcumin as feed additive in the diet of Oreochromis niloticus to improve its growth performance, health status and resistance against Aspergillus flavus. The control group was fed on a basal diet without nanocurcumin, and four diets T1, T2, T3 and T4 were supplemented with 10, 25, 40 and 55 mg/kg of nanocurcumin, respectively, in triplicate (20 fish/replicate). The duration of the feeding trial was 60 days. The final body weight, weight gain, specific growth rate and survival rate showed significantly (p < 0.05) increased values in the nanocurcumin groups than the control. Fish fed with nanocurcumin supplementation showed improvement in RBCs, haemoglobin, total protein, albumin and globulin while there was a decrease in the liver enzymes (AST and ALT), glucose and alkaline phosphatase. The creatinine was also decreased in fish fed nanocurcumin. The digestive enzymes amylase and lipase increased in the nanocurcumin‐treated groups, and the triglycerides values showed non‐significant increase, whereas the cholesterol values showed non‐significant decrease in T1 and T4. Meanwhile, the cortisol was nearly the same in all groups. At the end of the trial, the fish were challenged with Aspergillus flavus for 15 days. Aspergillus flavus resulted in the mortality of 100% of the control group and the groups with lower doses of nanocurcumin (T1 and T2) within the first week and second week post challenge respectively. In the treatments with high doses (T3 and T4), higher survival rates were recorded in a dose‐dependent manner. The pathogenicity of Aspergillus flavus was confirmed histopathologically. It was concluded that the dietary supplementation of nanocurcumin enhanced the health status of O. niloticus by improving the haemato‐immunological response and body composition parameters of the fish, and protected it from the Aspergillus flavus infection with optimum inclusion levels of 25–40 mg/kg diet.