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Hovenia acerba Lindl. (HA) was formerly used as a treatment for alcohol overdosing. To explore the mechanism of hepatoprotective effect of HA, the chemical components of Hovenia acerba Lindl. peduncles extract (HAPE) and Hovenia acerba Lindl. seeds extract (HASE) were compared by UPLC-QTOF-MS. Moreover, the alcohol damage model of human normal hepatocytes (LO2) and male Kunming mice were used to measure their effects on alcoholic liver damage. Results showed that HASE had 32 kinds of phenolic compounds, and the main components were caffeic acid, vitexin-2″-O-glucoside, ferulic acid hexoside, quercetin and its glycosides; HAPE had 24 kinds of phenolic compounds, and the main components were caffeic acid, kaempferol and chrysophano. The phenolic content of HASE (151.73 ± 12.66 mg gallic acid equivalent per gram of dry weight) (mg GAE/g DW) was higher than that of HAPE (17.89 ± 1.59 mg GAE/g DW). HASE and HAPE could increase the LO2 cell viability in the alcohol damage models. Moreover, the levels of triacylglycerol (TG), total cholesterol (TC), alanine aminotransferase(ALT), and aspartate aminotransferase (AST) were decreased, the activities of superoxide dismutase (SOD) and catalase (CAT) were increased, and the concentration of malondialdehyde (MDA) was decreased in both HASE and HAPE treated cell and mice groups. Results also showed that the concentration of reduced glutathione (GSH) and the activity of glutathione peroxidase (GSH-Px) were increased in mice. HASE and HAPE raised the mRNA expressions of nuclear factor erythroid-2 related factor 2 (Nrf2) and activated antioxidant-related genes: heme oxygenase-1 (HO-1), NADPH quinone acceptor oxidoreductase 1 (NQO1), and glutamate-cysteine ligase modifier subunit (GCLM), and enhanced the expression of Nrf2 and HO-1 proteins. HASE and HAPE could also increase antioxidant activity by enhancing Nrf2-mediated inducible expression of HO-1 to protect hepatocytes from injury. Furthermore, HASE showed better liver protective effect than HAPE. This study demonstrated the protective benefits of Hovenia acerba Lindl. peduncles and seeds extracts on alcoholic liver injury. [Display omitted] • HASE and HAPE showed important responsible for the hepatoprotective effect. • HASE had higher phenolic compound contents than HAPE. • HASE and HAPE ameliorate alcoholic liver injury via Nrf2/HO-1 signaling pathway. • HASE showed better liver protective effect than HAPE. [ABSTRACT FROM AUTHOR]