The present study aimed to investigate the effect of silver nanoparticles (AgNPs) (50 mg/L) on the behavioral changes, biochemical alterations, oxidative stress, and the histopathological changes in liver tissues of African catfish, clarias gariepinus. In addition to the potential role of  Nigella sativa (NS) in ameliorating these effects. Fish were divided into four groups: group 1 was control fed on the basal diet, group 2 was fed on 3% (NS) of basal diet, group 3 was exposed to 50 mg/L AgNPs, and group 4 was exposed to 50 mg/L AgNPs and fed on  3%  (NS) for 30 days.  Results revealed that catfish in the group (3) exposed to AgNPs exhibited changes in skin pigmentation and abnormal behavior in the swim.  A significant elevation (P<0.05) in levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) of catfish exposed to AgNPs compared to the control fish. Furthermore, a marked increase in hepatic lipid peroxidation (LPO), catalase (CAT), total antioxidant (TAC), glutathione (GSH), and superoxide dismutase (SOD) levels were recorded in the group (3). Alternatively, feeding exposed catfish to AgNPs on 3% (NS)  for 30 days, decreased the levels of ALP, AST, and ALT, improved the oxidative damage in liver tissues and attenuated the histological changes in hepatic tissues of C. gariepinus (group 4). Hence, this study suggested that (NS)  has hepatoprotective and antioxidant effects in African catfish against AgNPs toxicity.