BACKGROUND: Alcohol-induced liver injury (ALI) poses a significant threat to global human health. The Chinese Yi medicine Liangtoumao (LTM), which originated from the whole plant of Incarvillea arguta Royle (Royle), has been widely used by the Yi ethnic group to prevent and treat ALI and other liver diseases. However, its effectiveness and mechanisms are still under-researched. PURPOSE: The objective of our research is to investigate the chemical composition of LTM aqueous extract, evaluate its potential therapeutic intervention effect on ALI, and explore its mechanisms in rat models. METHODS: The chemical components and constituents of LTM aqueous extract migrating to the blood were analyzed by UPLC-Q-TOF/MS. Sprague-Dawley rats subjected to chronic binge alcohol exposure were utilized to establish chronic ALI models and evaluate the therapeutic effects of LTM aqueous extract. Serum and spatial metabolomics analyses were used to investigate potential mechanisms. RESULTS: A total of 60 chemical components in LTM aqueous extract were identified, with 67 absorbed into the blood, including 29 original compounds and 38 metabolites. Treatment with LTM aqueous extract remarkably alleviated hepatic lesions in livers of ALI rats, improved liver function, reduced oxidative stress and inflammation. Serum metabolomics and hepatic spatial metabolomics identified 30 and 215 differential metabolites, respectively. Metabolic pathways of glyoxylate and dicarboxylate, glycerophospholipid, linoleic acid, taurine and hypotaurine, and cysteine and methionine were closely related to the hepaprotective effects of LTM. CONCLUSION: Our research confirmed significant effects of LTM on ALI prevention and treatment for the first time. Metabolomic findings revealed that LTM significantly influences various aspects of lipid metabolism. This study supports expanded mechanism investigations of LTM and explores its possibility as a potential ALI therapy.