This　study　aimed　to　investigate　the　hypoglycemic　and　hypolipidemic　activities　of　polysaccharides　from　Grifola　frondosa　(GFP)　in　diabetic　mice　induced　by　high-fat　diet　(HFD)　and　streptozotocin　(STZ).　Results　showed　that　oral　administration　of　GFP　markedly　reduced　the　serum　levels　of　fasting　blood　glucose　(FBG),　oral　glucose　tolerance　(OGT),　cholesterol　(TC),　triglyceride　(TG)　and　low-density　lipoprotein　cholesterol　(LDL-C),　and　significantly　decreased　the　hepatic　levels　of　IC.　TG　and　free　fatty　adds　(FFA).　Meanwhile,　high-dose　of　GFP　supplementation　(900　mg/kg　day)　also　showed　powerful　effects　on　moderating　the　composition　of　intestinal　microflora　in　diabetic　mice,　especially　altering　the　functionally　relevant　intestinal　microbial　phylotypes.　Spearman＇s　correlation　network　analysis　revealed　that　key　microbial　phylotypes　responding　to　GFP　intervention　were　strongly　correlated　with　the　glucose　and　lipid　metabolic　disorders　associated　parameters.　Moreover,　GFP　treatment　regulated　mRNA　expression　levels　of　the　genes　responsible　for　hepatic　glucose　and　lipid　metabolism.　It　is　noteworthy　that　GFP　treatment　markedly　increased　mRNA　expression　of　cholesterol　7　alpha-hydroxylase　(CYP7A1)　and　bile　salt　export　pump　(BSEP),　suggesting　an　enhancement　of　bile　acids　(BAs)　synthesis　and　excretion　in　liver.　These　findings　demonstrated　that　GFP　could　prevent　hyperglycemia　and　hyperlipidemia　in　diabetic　mice　by　altering　gut　microbiota　and　regulating　hepatic　glycolipid　metabolism　related　genes,　and　therefore　could　be　used　as　potential　functional　food　ingredients　for　the　prevention　or　treatment　of　hyperglycemia　and　hyperlipidemia.　(C)　2019　Elsevier　B.V.　All　rights　reserved.