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Forty compounds were isolated and characterized from <i>A. tenuissimum</i> flower. Among them, twelve flavonoids showed higher α−glucosidase inhibition activities in vitro than acarbose, especially kaempferol. The molecular docking results showed that the binding of kaempferol to α−glucosidase (GAA) could reduce the hydrolysis of substrates by GAA and reduce the glucose produced by hydrolysis, thus exhibiting α−glucosidase inhibition activities. The in vivo experiment results showed that flavonoids−rich <i>A. tenuissimum</i> flower could decrease blood glucose and reduce lipid accumulation. The protein expression levels of RAC−alpha serine/threonine−protein kinase (AKT1), peroxisome proliferator activated receptor gamma (PPARG), and prostaglandin G/H synthase 2 (PTGS2) in liver tissue were increased. In addition, the Firmicutes/Bacteroidetes (F/B) ratio was increased, the level of gut probiotics <i>Bifidobacterium</i> was increased, and the levels of <i>Enterobacteriaceae</i> and <i>Staphylococcus</i> were decreased. The carbohydrate metabolism, lipid metabolism, and other pathways related to type 2 diabetes mellitus were activated. This study indicating flavonoids−rich <i>A. tenuissimum</i> flower could improve glycolipid metabolic disorders and inflammation in diabetic mice by modulating the protein expression and gut microbiota.