Selenium (Se) is an essential trace element for mammals. Inadequate Se can aggravate the development of inflammatory bowel diseases (IBD). Selenium nanoparticles (SeNPs) are characterized by low toxicity and anti-inflammatory properties with functional modifications. In this study, we attached SeNPs with natural polysaccharides from Poria cocos polysaccharide (Pachyman, PYN), which has an anti-inflammatory effect. Herein, we explored PYN-SeNPs potential beneficial effects on IBD by the mice model subjected to acute colitis.