Nowadays, nanomaterials enter high numbers of daily used products and drug manufacture. A nanocomposite of vitamins C (VC) and vitamin E (VE) with chitosan as a vehicle and protector was used in a comparative eight-week feeding study, Nile tilapia weighing 31.2 ± 0.36 g distributed in seven groups and fed (G1) basal diet, (G2) bulk VC, (G3) VC- nanoparticles (NPs), (G4) bulk VE, (G5) VE-NPs, bulk VCE (G6), and (G7) VC plus VE (VCE)-NPs, respectively. The Nile tilapia-fed nanocomposite vitamins had significantly higher growth performance compared to the control; VCE-NPs had the superiority among tested supplementations where total weight gain (63.6 g), daily weight gain (1.13 g), relative growth rate (206.1%) with lower feed conversion rate (1.6) and insignificant feed intake (101.5 g). Overall, the level of liver enzymes was significantly decreased in fish serum after eight-week nanocomposite supplementation, and dietary VCE-NPs caused a significant reduction of serum AST (18.45 IU/L) and ALT (14.77 IU/L) compared to the control 25.5 IU/L and 17.6 IU/L, respectively. Fish fed dietary VCE-NPs, VC-NPs, and VE-NPs had significant enhancement of RBCs 4.2 × 106/μL, 3.8 × 106/μL, and 3.55 × 106/μL; WBCs 46.15 × 103, 42.9 × 103, and 44 × 103/μL, respectively, Also TP was significantly higher 6.38 g/dL in VCE-NPs group compared to the control and the other treatments. Over all, the dietary nanocomposite vitamins boost the innate immunity of the experimental Nile tilapia, the oxidative burst activity (OBA), phagocytic activity (PA), phagocytic index (PI), and serum antibacterial (SAA) were significantly increased compared to those received bulk vitamins and the control. The activity of antioxidant biomarkers in fish serum including glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), glutathione reductase (GR), and myeloperoxidase (MPO) showed a rise in the serum of Nile tilapia received nano- and bulk-form of VC and VCE compared to the control and both forms of VE. Furthermore, the level of malondialdehyde (MDA), reduced glutathione (GSH), and oxidized glutathione (GSSG) were significantly increased in the fish serum following the trend of antioxidants enzymes. In conclusion, a dietary nanocomposite of vitamin C and vitamin E enhanced Nile tilapia's growth performance and feed utilization. It could also improve health status and immune response. The values of antioxidant biomarkers indicated that the nanocomposite could help the fish body scavenge the generated reactive oxidative species (ROS).