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• Characterization and quantitation evaluation of Artemisia argyi by HPLC-DAD-Q-TOF-MS were reported. • The blood glucose level, oral glucose tolerance and small intestinal α -glucosidase inhibitory tests were assessed. • The analysis of the total phenolic content (TPC), antioxidant and α -glucosidase inhibitory was measured. • Four characteristic compounds were elucidated by molecular docking. Diabetes is one of the metabolic disorders in the world. It is the prime reason of mortality and morbidity owing to hyperglycemia which is link with numerus obstacles. Artemisia argyi is commonly used as an ingredient in healthy foods as well as an herbal medicine in Asian countries. The present research aims to evaluate the hypoglycemic effects of A. argyi and reveal its the potentially active constituents. The chemical composition was identified by HPLC-DAD-Q-TOF-MS, and fractionation was performed by extraction. The fractions were assessed by the blood glucose level, oral glucose tolerance and small intestinal α -glucosidase inhibitory tests, and an analysis of the total phenolic content (TPC), antioxidant and α -glucosidase inhibitory activities. In our efforts to characterize the compounds responsible for hypoglycemic effect, bioactivity-guided fraction of the MeOH extract and chemical investigation of its active EtOAc fraction led to the successful identification of caffeoylquinic acids, which were elucidated by molecular docking, using the crystal structure of S. cerevisiae isomaltase (PD code: 3AXI). In summary, this bio-guided search revealed that caffeoylquinic acids from A. argyi as potential active constituents displayed with hypoglycemic activity, which provided a basis for further study of pharmacological activity. [ABSTRACT FROM AUTHOR]