The present study was conducted to investigate the protective effect of Chitosan nanoparticles (CSNPs) on the behavioral, biochemical alterations, and oxidative stress biomarkers of African catfish, Clarias gariepinus exposed to (1.43µg/L)  Bisphenol-A (BPA) for 30 days. Fish were allocated to five groups as follows: group I was the control, group II was treated with Chitosan nanoparticles (0.66ml/L) , group III  was treated with BPA (1.43µg/L), group IV was treated with BPA (1.43µg/L) plus CSNPs (0.33ml/L), group V was treated with BPA (1.43µg/L) plus CSNPs (0.66ml/L). At the end of the experiment, biochemical and oxidative stress biomarkers were analyzed in the blood and kidney tissues. Serum alanine aminotransferase (ALT), total proteins, albumin, globulin, Alkaline Phosphatase (ALP), Acetylcholinesterase (AChE) showed a  significant decrease in group III when exposed to BPA compared to (group I). Meanwhile, Cortisol, Glucose, Urea, Creatinine, Uric acid, Aspartate aminotransferase (AST) increased in catfish exposed to (1.43µg/L) BPA  compared to the control fish. Marked increments in renal Superoxide dismutase (SOD) and malondialdehyde (MDA) levels and significant reductions in the activity of renal Glutathione peroxidase (GSH-Px) , total antioxidant capacity (TAC), and Catalase (CAT) were detected in BPA- exposed fish  (group III) compared to the control group (group I) and CNPs (0.66ml/L.) (group II). However, administration of fish with the two tested doses (0.33 and0.66ml/L) of CSNPs attenuated the BPA- induced biochemical changes oxidative stress in catfish. Such improvement was more obvious in catfish that received the higher dose (0.66ml/L) of CSNPs, whereas the tested parameters were restored to the control group in comparison to catfish exposed to BPA alone (group III) after 30 days of exposure. The obtained results induced that CSNPs administration ameliorated the toxic effects of BPA on African catfish.