Abstract: A selenized polysaccharide (Se-SCP) with selenium content of (7.19±0.067) mg/g was synthesized by imidazole-mediated method using sweet corncob polysaccharide (SCP) as raw material. In order to explore the inhibitory effect of Se-SCP on non-enzymatic glycosylation reaction, fructose and bovine serum albumin (BSA) were selected as substrates to establish albumin/fructose simulation system. Fructosamine→α-dicarbonyl compounds→advanced glycation end products (AGEs), the three characteristic products in the non-enzymatic glycosylation process, were determined and analyzed by transmission electron microscopy (TEM) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The effects of protopolysaccharides and selenium polysaccharides on the non-enzymatic glycosylation process were compared and analyzed in terms of microstructure. The results showed that Se-SCP had different degrees of inhibition on the three stages of protein non-enzymatic glycosylation process, and the inhibition rates of characteristic products in non-enzymatic glycosylation process reached 89.5%, 74.9% and 71.7%, respectively. In terms of inhibiting protein cross-linking structure, compared with the SCP group, the texture of Se-SCP was relatively clear, the structural density was small, and the inhibition effect was obvious. The results of SDS-PAGE showed that Se-SCP reduced the formation of high molecular weight cross-linked protein induced by fructose, and the effect of Se-SCP was better, which was similar to that of positive drug. In summary, Se-SCP has good anti-nonenzymatic glycation activity and has great potential in inhibiting diabetes and its complications.