Acute liver disease may develop due to various causes and occur by different mechanisms. Carbon tetrachloride (CCl₄), a well-known hepatic toxicant, was selected as a model of alkylating agents that do not induce glutathione depletion. Our previous study indicated CCl₄-induced hepatotoxicity was decreased by pretreatment with the Japanese herbal medicine “Juzen-taiho-to” (JTX), suggesting that prophylaxis with JTX protects mice from CCl₄-induced acute hepatic toxicity. In contrast, bromobenzene (BB) is a known glutathione-depleting agent. Although BB-induced hepatotoxicity also promotes lipid peroxidation, the mechanism of hepatic injury is different from that of CCl₄. Hence, in this study, we investigated whether pretreatment with JTX ameliorated BB-induced hepatotoxicity. Mice injected with BB showed increased plasma levels of hepatic injury markers (alanine aminotransferase and aspartate aminotransferase) in addition to hepatic lipid peroxidation. Pretreatment with JTX decreased BB-induced plasma levels of hepatic injury markers. BB-induced hepatotoxicity is mainly caused by oxidative stress. JTX pretreatment also decreased BB-induced lipid peroxidation. Our results suggest that JTX has the potential to protect against BB-induced hepatotoxicity and modulate oxidative stress.