Kushenol I is a bioactive compound exhibiting anti-inflammatory, antioxidant, and ulcerative colitis–ameliorating effects, demonstrated in a DSS-induced UC mouse model where oral administration improved colon length, body weight, and disease scores while reducing pro-inflammatory cytokines including IL-1β, IL-6, IL-17, and TNF-α. Kushenol I increase IL-10 expression, inhibited key inflammatory signaling proteins such as AKT, p38 MAPK, PI3K, NLRP3, FOXO1, and TLR4, enhancing intestinal barrier integrity. Kushenol I positively modulate gut microbiota, and elevated splenic T-cell proportions, supporting therapeutic potential in inflammatory bowel disease.