This study evaluates the hepatoprotective effect of carotenoids against isoniazid (INH) and rifampicin (RIF). Thirty-six adult rats were divided into the following 4 groups: (1) control group treated with normal saline; (2) INH + RIF group treated with 50 mg·(kg body mass)-1·day-1 of INH and RIF each; (3) INH + RIF+ carotenoids group treated with 50 mg·(kg body mass)-1·day-1 of INH and RIF each and 10 mg·(kg body mass)-1·day-1 of carotenoids; and (4) carotenoids group treated with 10 mg·(kg body mass)-1·day-1 of carotenoids for 28 days intragastrically. Oxidative stress and antioxidant levels in liver and blood, liver histology and change in transaminases were measured in all the above-mentioned groups. There was an increase in lipid peroxidation with a reduction in thiols, catalase, and superoxide dismutase (SOD) in the liver and blood of rats accompanied by an increase in transaminases, bilirubin, and alkaline phosphatase. Treatment with carotenoids along with INH + RIF partially reversed lipid peroxidation, thiols, catalase, and SOD in the liver and blood of rats. Elevated levels of the enzymes in serum were also reversed partially by this treatment. The degree of necrosis, portal triaditis, and inflammation were also lowered in the carotenoids group. In conclusion, carotenoids supplementation in INH + RIF treated rats showed partial protection.