Bisphenol S (BPS), a BPA analog and a safer alternative, is utilized in a diverse range of industrial applications, such as making polycarbonate plastics, epoxy resins, thermal receipt papers, and currency bills. Recently, the increased use of BPS in containers and packages for daily life has been interrogated due to its identical chemical structure and probable endocrine‐disrupting actions as BPA has. The present study aimed to evaluate the alterations in biochemical indices and antioxidant enzymes as certain indicators of the endocrine‐disrupting effect of BPS in Channa striatus, a freshwater fish. BPS‐exposed fish species were subjected to three sub‐lethal concentrations of BPS (1, 4, and 12 ppm) and observed after an interval of 7 and 21 days. Exposure to BPS caused a reduction in the level of protein in muscle, gonads and the liver due to an impairment of protein synthesis. Levels of cholesterol in the muscle, gonads, and liver of BPS‐exposed fish were found to be decreased after treatment, indicating either an inhibition of cholesterol biosynthesis in the liver or reduced absorption of dietary cholesterol. The levels of antioxidant enzymes such as superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase showed remarkable increases, while the activity of glutathione S‐transferase decreased considerably, indicating the antioxidant defense mechanism to counteract the oxidative stress induced by BPS. Moreover, a significant increase was noted in the level of lipid peroxidation products, like malondialdehyde and conjugate diene, which represent biomarkers of oxidative stress. The histoarchitecture changes were also observed in the liver, muscle and gonads of BPS‐treated fish species. The present study showed that sub‐lethal exposure to BPS significantly influenced the activities of these enzymes and peroxidation byproducts. From this study, it is concluded that BPS‐caused toxic effects in fish species lead to an imbalance in the antioxidant defense system. It is clearly indicated that BPS toxicity could lead to susceptible oxidative stress in various tissues and could damage vital organs.