Ulcerative colitis (UC) is a chronic, nonspecific inflammatory bowel disease that is very difficult to cure. In this study, we have designed and synthesized a series of new 1,2,3-triazole-linked (±)-Agrimonolide derivatives and evaluated their anti-inflammatory activities. The in vitro results demonstrated that most triazole derivatives effectively inhibited NO production, and most compounds exhibited better anti-inflammatory activity than that of (±)-Agrimonolide and positive drug Dexamethasone. The further in vivo tests indicated that 6d could inhibit the release of inflammatory mediators in the colon tissue and alleviate Ulcerative colitis by inhibiting JAK1/STAT3 pathways.