Abstract: Artemisia argyi polysaccharide gelatin microspheres were prepared by emulsification-chemical crosslinking method using gelatin as the boating material. The effects of the concentration of Artemisia argyi polysaccharide, gelatin mass fraction, oil-water ratio, and emulsifier concentration on the encapsulation rate and drug loading capacity of the microspheres were investigated. The optimal preparation prescription was determined by single-factor and response surface analysis. The morphology of Artemisia argyi polysaccharide gelatin microspheres was observed by scanning electron microscope (SEM). The slow-release effect and the inhibition of α-glucosidase and α-amylase activities were investigated by the determination of release degree. The results showed that the optimal prescription was as follows: The concentration of Artemisia argyi polysaccharide 15 mg/mL, oil-water ratio 3.8:1, emulsifier concentration 1.2% and the gelatin mass fraction 10.20%, and the encapsulation rate and drug loading capacity was 63.80% and 9.38% respectively. Under the SEM, the microspheres appeared round and the average particle size was 59.593 μm. The results of release degree showed that the cumulative release rate of Artemisia argyi polysaccharide was about 60% and 80% at 12 h in pH 2.5 (simulated gastric acid) and 7.4 (simulated intestinal fluid) media, respectively. The inhibition of α-glucosidase and α-amylase by microspheres releasing polysaccharides in pH7.4 release medium was 31.31% and 17.15%, respectively. It was demonstrated that the microspheres prepared from Artemisia argyi polysaccharide and gelatin had an enteric slow-release effect and specific in vitro hypoglycemic activity, which provided a theoretical basis for the development of the products of Artemisia argyi polysaccharide for regulating blood glucose.