Abstract: Objective: Oyster peptide (OYS), pueraria lobata, and licorice exhibit diverse biological activities. The combination of these components in a specific ratio to form the oyster peptide-pueraria lobata-licorice compound (OPL) has the potential to alleviate alcoholic liver damage (ALD). This study aims to evaluate the anti-hangover effects of OPL in mice and its restorative effects on those with alcoholic liver injury, while also exploring the underlying mechanisms through transcriptomic analysis. Methods: Male Kunming mice were randomly assigned to seven groups, each consisting of ten mice: the control group (CON), model group (MOD), positive drug group (POS) at a concentration of 25 mg/mL, oyster peptide group (OYS) at 40 mg/mL, low-dose oyster peptide-Pueraria-Glycyrrhiza complex group (LOD) at 20 mg/mL, medium-dose oyster peptide-Pueraria-Glycyrrhiza complex group (MED) at 40 mg/mL, and high-dose oyster peptide-Pueraria-Glycyrrhiza complex group (HD) at 80 mg/mL. The alcohol-relieving effects and liver injury repair activities were assessed in the mice. Histopathological analysis of liver tissues was conducted using HE-stained liver sections, and the potential mechanisms for improving ALD were further analyzed through transcriptomics. Results: Compared to the model group, the OPL group significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, as well as levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in mice (P<0.01). Specifically, ALT activity in the OPL group decreased by up to 34.16%, and AST activity decreased by up to 41.47%. Furthermore, minimal lipid droplet accumulation and nuclear pyknosis were observed in the liver cells of mice treated with OPL. Transcriptomic analysis revealed that OPL may exert its pharmacological effects in preventing and treating alcoholic liver injury by enhancing the expression of the ELOVL fatty acid elongase 6 gene (ELOVL 6) in the unsaturated fatty acid biosynthesis pathway during lipid metabolism. Conclusion: This study preliminarily demonstrates that OPL possesses certain capabilities in alleviating alcohol intoxication and repairing alcoholic liver injury.