In this study, the ultrasonic-assisted ionic liquid extraction of Artemisiae argyi leaves flavonoids was optimized using single-factor tests and the response surface method, and its antioxidant and hypoglycemic activities were determined in vitro. The results showed that the optimal process parameters for the extraction of A. argyi leaf flavonoids as follow: 8 g/L 1-Butyl-3-methylimidazolium Bromide ([C4mim]Br) as extraction solvent, ultrasonic time of 68 min, and material-liquid ratio of 1:30 g/mL. Under the optimized conditions, the yield of A. argyi leaf flavonoids was 14.36%. In vitro antioxidant assay showed that A. argyi leaf flavonoids have good scavenging abilities against 1,1-diphenyl-2-trinitrophenylhydrazine radicals (DPPH ?), 2,2-diazo-di (3-ethylbenzothiazole-6-sulfonic acid) diamine salts (ABTS+), and ?OH, with a corresponding half inhibitory concentration (IC50) of 0.15, 0.12 and 0.6 mg/mL, respectively. In vitro hypoglycemic assay showed that A. argyi leaf flavonoids have the inhibitory effect on α-amylase and α-glucosidase, with the IC50 value of 0.59 and 0.37 mg/mL, respectively. The flavonoids of A. argyi leaf had good antioxidant properties and hypoglycemic activity.