Bisphenol S is an emerging pollutant that is contaminating aquatic ecosystems and causing detrimental effects on aquatic organisms, especially fish. Therefore, the study was designed to evaluate the toxicity of bisphenol S (BPS) through genotoxic, biochemical, histopathological, and oxidative damage in the liver, gills, and kidneys of Labeo rohita fish. Fish were exposed to three different concentrations (400 µg/L, 800 µg/L, and 1000 µg/L) of BPS for 21 days. A significant (p ≤ 0.05) decline in antioxidant enzymatic activity of superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), and peroxidase (POD) was observed in all tissues, whereas elevation in oxidative contents (TBARS and ROS) was observed. Comet analysis showed elevated olive tail moment and % of DNA damage. Light microscopy revealed several anomalies including cluster nuclei formation, damaged parenchyma cells, sinusoidal spaces, and melanomacrophage in the kidney, sinusoidal spaces, dilated hepatic vein, pyknotic nuclei, melanomacrophage, and cell necrosis in the liver and bone cell deformities, lamellar aneurysm, hyperplasia, and curved secondary gill lamellae in gills. Results of hematobiochemical analysis revealed a significant (p ≤ 0.05) increment in hematocrit, WBCs, cholesterol, blood glucose, triglycerides, AST, ALT, T