Inhibitory mode and anti-diabetic activities of the Carols muscadine extracts on the α-glucosidase and pancreatic lipase were investigated. The IC₅₀ values of the muscadine and its seed methanolic extracts against the α-glucosidase were 1.92 and 1.53 mg/mL, and those against the lipase were 34.41 and 8.63 mg/mL, respectively, which indicated the muscadine possessed the strong anti-diabetes activity. Particularly, the ethyl acetate (EtOAc) extract fractions exhibited the highest inhibitory activities against both enzymes. Since most of the phenolic compounds existed in the EtOAc fractions, it is suggested that phenolic compounds may be the main source against the α-glucosidase and pancreatic lipase. Twelve individual phenolics were identified by HPLC-MS. Ellagic acid and quercetin exhibited much stronger anti-diabetic activities among the selected phenolic standards. Besides, the extracts and the phenolic standards obeyed the competitive mode in their enzymatic inhibitions.