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Excessive alcohol consumption can lead to serious health complications, with liver and neurological complications being the most important. In Western nations, alcoholic liver disease accounts for 50% of mortality from end-stage liver disease and is the second most common cause of liver transplants. In addition to direct damage, hepatic encephalopathy may also arise from alcohol consumption. However, effective treatment for liver disease, as well as neurological injury, is still lacking today; therefore, finding an efficacious alternative is urgently needed. In the current study, the preventive and therapeutic effects of Schisandrin B (Sch B) against ethanol-induced liver and brain injuries were investigated. By using two treatment models, our findings indicated that Sch B can effectively prevent and ameliorate alcoholic liver diseases, such as resolving liver injuries, lipid deposition, inflammasome activation, and fibrosis. Moreover, Sch B reverses brain damage and improves the neurological function of ethanol-treated mice. Therefore, Sch B may serve as a potential treatment option for liver diseases, as well as subsequential brain injuries. Furthermore, Sch B may be useful in preventive drug therapy against alcohol-related diseases.