The aim of this study was to investigate whether the Japanese herbal medicine “Juzen-taiho-to (JTX)” has a protective effect on ethanol (EtOH)-induced liver injury. Seven-week-old male ICR mice were orally administered JTX or saline once a day for three days. Twenty-four hours after the last administration, the mice were intraperitoneally injected with EtOH (2 g/kg). The mice in each group were killed 24 hr after EtOH administration and were bled to obtain plasma. The mice injected with EtOH had high plasma levels of alanine aminotransferase and aspartate aminotransferase and lipid peroxidation. Histopathological examination of the liver of mice treated with EtOH revealed an abnormal outline around the central vein, glycogen depletion, and expression of prostaglandin-endoperoxide synthase 2. Pretreatment with JTX prevented the EtOH-induced increase in the levels of alanine aminotransferase and aspartate aminotransferase, lipid peroxidation, and histopathological changes. Our results suggest that JTX exerts protective effects against EtOH-induced liver disease by modulating oxidative stress and inflammatory response.