Abstract: This study investigated the hepatoprotective effects and mechanisms of fermented Angelica keiskei (FAK), produced through synergistic fermentation using Lactobacillus plantarum and Saccharomyces cerevisiae, against alcohol-induced liver injury in mice. Male Kunming mice were randomly divided into seven groups (n=12 per group): normal control, model control, silibinin-treated, freeze-dried Angelica keiskei powder, and low-, medium-, and high-dose FAK groups. Alcohol-induced liver injury was established via 30-days intragastric administration of edible alcohol, with body weight monitored periodically. Post-intervention assessments included serum lipid profiles, organ indices, hepatic injury markers, antioxidant enzymes, inflammatory cytokines, and gut microbiota alterations. Results demonstrated that FAK significantly attenuated alcohol-induced weight loss (P<0.05) and reduced hepatic index, serum lipid levels, and hepatic injury markers. FAK intervention notably decreased hepatic lipid accumulation while enhancing antioxidant capacity, as evidenced by increased glutathione peroxidase (GSH-Px) activity and reduced malondialdehyde (MDA) concentrations (P<0.05). Concurrently, FAK suppressed pro-infammatory cytokine production. Mechanistic analyses revealed that FAK restored the Firmicutes-Bacteroidetes (F/B) ratio to near-normal levels and ameliorated alcohol-induced phylum- and genus-level dysbiosis. These microbial modifications were associated with reduced endotoxin production and enhanced intestinal barrier integrity, Intestinal homeostasis here refers to the restoration of relative stability in microbial community function (e.g., barrier protection, metabolic balance) rather than an identical composition to the normal group, suggesting gut microbiota modulation as a potential pathway for FAK-mediated hepatoprotection. This study provides a theoretical foundation for the high-value utilization of Angelica keiskei resources and its potential application in functional foods targeting alcohol-related hepatic disorders.