A plant-derived compound found in Hudi enteric-coated capsule (HDEC) may offer a new way to rebalance immune responses in ulcerative colitis (UC). In mouse models of chronic intestinal inflammation, HDEC and its major bioactive constituent, polydatin, reduced disease severity and mucosal injury. The study traced polydatin's action to Kelch-like ECH-associated protein 1 (KEAP1), which directly binds to activate nuclear factor erythroid 2-related factor 2 (NFE2L2) signaling. This lowered reactive oxygen species (ROS), restrained inflammatory T helper 1 (Th1) and T helper 17 (Th17) cell development, and promoted regulatory T (Treg) cells. The same immune-regulating pattern was also observed in human cells and UC mucosal samples.