The work aims to optimize the preparation process of SeSCP-80-I with sweet corncob polysaccharide as raw material and selenium content as indicator, and explore the effect of sweet corncob selenium polysaccharide on inhibiting the activity of α-amylase and α-glucosidase which affect the key enzymes of starch digestion of glucosidase. On the basis of single factor experiment, the process conditions were optimized by response surface method. The content of selenium was determined by hydride generation atomic fluorescence spectrometry, and its structure was determined by infrared spectroscopy. The results showed that the selenium content could reach 3.717 mg/h when the reaction temperature was 86 ℃, the raw material ratio (mass ratio of SCP-80-I and Na2SeO3) was 1∶0.91, the nitric acid concentration was 0.54% (volume fraction), and the reaction time was 6.4 h. The Se—O—C characteristic absorption peak and SeO32− characteristic absorption peak of the prepared sweet corncob se polysaccharide indicated that the combination formed stable selenium derivatives. In addition, the IC50 values of selenium modified sweet corncob polysaccharide on α-amylase and α-glucosidase were 5.495 mg/mL and 2.687 mg/mL respectively, which were better than those of non selenium modified sweet corncob polysaccharide on α-amylase and α-glucosidase. The selenium polysaccharide of corncob has good hypoglycemic activity.