Alcoholic liver injury (ALI) has emerged as a significant public health concern, necessitating the urgent identification of medicinal-food resources for its prevention and treatment. As a natural medicinal food resource, Chenpi (CHE) is rich in various flavonoid bioactive compounds and exhibits potential antioxidant, anti-inflammatory, and hepatoprotective effects. However, the effect and mechanism of CHE in preventing and improving ALI are not yet known. This study sought to elucidate CHE’s hepatoprotective mechanisms in ALI from the biochemical markers, microbiome and transcriptome perspectives. Results showed that CHE ameliorated ALI by improving oxidative stress, inflammatory cytokines and liver function. 16S rRNA analysis revealed that CHE alleviated ALI pathological progression primarily by restoring gut microbiota composition. Transcriptomic analysis showed that CHE improved ALI mainly related to MAPK signaling pathway. Pearson correlation analysis revealed that Candidatus_Saccharimonas, Turicibacter, and Clostridium_sensu_stricto_1 play key roles in the process by which CHE ameliorates alcohol-induced inflammation and pathological angiogenesis. These findings revealed that CHE has the potential to be used as a functional food to prevent or improve ALI.