ABSTRACT Nano-sized essential minerals and nutrients synthesized from plant extracts are being explored for their impact on growth, immune stimulation, and overall fish health. This study evaluated the growth performance, health, and survival of African catfish, Clarias gariepinus, particularly when challenged with Aeromonas hydrophila. Biosynthesized Aloe vera leaf iron oxide nanoparticles (ANP) were confirmed by ultra-violet spectroscopy, Fourier-transform infrared spectroscopy, and scanning electron microscopy as nanoparticles. The ANPs were added to the basal diet at 0, 40, 80, 120, and 160 mg/kg, forming five treatments. The fish were fed to apparent satiation twice daily for 84 days. Results showed that dietary ANP improved weight gain, specific growth rate, protein efficiency ratio, and feed conversion ratio significantly with increasing levels of the nanoparticles. Fish fed 160 mg/kg ANP diet had a weight gain of 102.12 ± 18.91 g, while fish fed the control diet had a weight gain of 78.89 ± 22.2 g. Fish quality indices, including head-to-body percentage, visceral-somatic ratio, and flesh ratio, were similar (p > .05) across treatments. Supplementation of ANP improved significantly fish carcass quality and survival rate compared to the control diet. Fish fed nanoparticle diets had significantly different (p < .05) moisture, ash, and protein contents across all treatments. The fat content decreased with increasing nanoparticle levels, with the control diet showing the highest value (14.54%) and 160 mg/kg ANP diet the lowest (12.94%). Dietary ANP also improved carcass iron and zinc contents significantly. Additionally, ANP increased packed cell volume, red blood cells, white blood cells, hemoglobin, and erythrocyte sedimentation count more than the control diet. Alanine transferase, aspartate transferase, catalase, and superoxide dismutase levels increased with ANP in the diets. Fish-fed ANP diets had higher (p < .05) total serum protein than fish fed the control diet. ANP diets reduced blood glucose levels significantly, and cholesterol levels decreased marginally with increasing nanoparticle levels. Conclusively, ANP positively influenced the growth, immunity, and survival of C. gariepinus.