Monascus-fermented　red　mold　rice　(RMR)　has　excellent　physiological　efficacy　on　lipid　metabolism　and　liver　function.　This　study　investigated　the　ameliorative　effects　of　monascuspiloin　(MP)　from　RMR　on　alcoholic　liver　injury　in　mice,　and　further　clarified　its　mechanism　of　action.　Results　showed　that　MP　intervention　obviously　ameliorated　lipid　metabolism　and　liver　function　in　mice　with　over-drinking.　In　addition,　dietary　MP　intervention　reduced　liver　MDA　levels　and　increased　liver　CAT,　SOD,　and　GSH　levels,　thus　alleviating　liver　oxidative　stress　induced　by　excessive　drinking.　16S　rRNA　amplicon　sequencing　showed　that　MP　intervention　was　beneficial　to　ameliorate　intestinal　microbiota　dysbiosis　by　elevating　the　proportion　of　norank_f_Lachnospiraceae,　Lachnoclostridium,　Alistipes,　Roseburia,　Vagococcus,　etc.,　but　decreasing　the　proportion　of　Staphylococcus,　norank_f_Desulfovibrionaceae,　Lachnospiraceae_UCG-001,　Helicobacter,　norank_f_Muribaculaceae,　unclassified_f_Ruminococcaceae,　etc.　Additionally,　correlation　network　analysis　indicated　that　the　key　intestinal　bacterial　taxa　intervened　by　MP　were　closely　related　to　some　biochemical　parameters　of　lipid　metabolism,　liver　function,　and　oxidative　stress.　Moreover,　liver　metabolomics　analysis　revealed　that　dietary　MP　supplementation　significantly　regulated　the　levels　of　75　metabolites　in　the　liver,　which　were　involved　in　the　synthesis　and　degradation　of　ketone　bodies,　taurine,　and　hypotaurine　metabolism,　and　other　metabolic　pathways.　Furthermore,　dietary　MP　intervention　regulated　gene　transcription　and　protein　expression　associated　with　hepatic　lipid　metabolism　and　oxidative　stress.　In　short,　these　findings　suggest　that　MP　mitigates　alcohol-induced　liver　injury　by　regulating　the　intestinal　microbiome　and　liver　metabolic　pathway,　and　thus　can　serve　as　a　functional　component　to　prevent　liver　disease.　©　2022　by　the　authors.