Red　yeast　rice　(RYR)　has　been　extensively　used　as　a　natural　food　for　thousands　of　years　and　still　plays　an　important　role　in　the　world　food　industry.　In　this　study,　the　protective　effect　and　the　mechanism　of　monaphilone　B　(MB)　from　RYR　on　alcoholic　liver　injury　were　investigated　in　mice.　The　results　showed　that　MB　effectively　ameliorated　alcohol-induced　liver　lipid　metabolism　(decreasing　serum　total　cholesterol　[TC],　triglyceride　[TG],　low-density　lipoprotein　cholesterol　[LDL-C],　and　increasing　high-density　lipoprotein　cholesterol　[HDL-C]),　oxidative　stress　(decreasing　hepatic　maleic　dialdehyde　[MDA]　level,　increasing　catalase　[CAT],　superoxide　dismutase　[SOD],　alcohol　dehydrogenase　[ADH]　and　glutathione　[GSH]　hepatic　activities),　and　inflammatory　response　(decreasing　hepatic　lipopolysaccharide　[LPS],　tumor　necrosis　factor-α　[TNF-α],　Interferon-γ　[IFN-γ]　and　interleukin　6　[IL-6]),　repaired　liver　function　(reducing　serum　alanine　aminotransferase　[ALT],　aspartate　aminotransferase　[AST],　and　liver　lactate　dehydrogenase　[LDH]　activity).　16S　amplicon　sequencing　showed　that　MB　administration　effectively　modulated　intestinal　flora　and　its　metabolism,　which　were　highly　correlated　with　the　improvement　of　liver　function　and　intestinal　barrier　function.　Liver　metabolomics　analysis　indicated　that　MB　administration　regulated　69　liver　potential　biomarkers　involved　in　glycerophospholipid　metabolism,　nicotinate　and　nicotinamide　metabolism,　tryptophan　metabolism,　and　so　on.　Reverse　transcription-quantitative　polymerase　chain　reaction　(RT-qPCR)　and　Western　blot　(WB)　analysis　revealed　that　MB　administration　modulated　gene　transcription　and　protein　expression　related　to　liver　lipid　metabolism　and　oxidative　stress.　These　findings　provide　scientific　evidence　that　MB　has　the　biological　activity　to　ameliorate　alcohol-induced　lipid　metabolism　disorders,　liver　oxidative　stress,　and　enterobacterial　dysbiosis.　©　2025　The　Author(s).　eFood　published　by　John　Wiley　&　Sons　Australia,　Ltd.　on　behalf　of　International　Association　of　Dietetic　Nutrition　and　Safety.