The positive effects of feeding nano-curcumin and Spirulina platensis on O. niloticus's growth performance, hepatoprotective ability, antioxidant response, immunity, digestibility, and organ histopathology were predicted by this study. Nile tilapia fingerlings (n = 180 fish; 10 ± 0.5 g) were divided into three groups (three replicates/group) and fed diets containing zero percent (control), 30 mg kg-1 curcumin nanoparticles (Cu-NPs group), and 5 g kg-1 Spirulina platensis (SP group). Growth performance, haematological, antioxidant, biochemical, and immunological markers plus histological changes were evaluated after the feeding study lasted 56 days. Our results revealed that Cu-NPs and SP have favorable effects on carcass composition, growth performance, hematological, and biochemical parameters. Moreover, Cu-NPs and SP supplementation significantly elevated serum Ig M level (p < 0.01, p < 0.05), lysozyme (p < 0.001), amylase (p < 0.05, p < 0.01), lipase (p < 0.05) and protease (p < 0.01) activities unlike the control group. Additionally, significant elevation of SOD (p < 0.001) and GPx (p < 0.01, p < 0.05) activities with diminished MDA (p < 0.001, p < 0.01) production was noticed in SP and Cu-NPs groups compared to control one. Overall, diets supplemented with Cu-NPs and SP effectively improved the growth performance, hepatic function, immune response, and antioxidant impacts in Nile tilapia fingerlings.