BACKGROUND: Exochorda racemosa is a member of the genus Exochorda in the Rosaceae family. Its tender leaves and buds are favored as a unique wild vegetable by people in central China. PURPOSE: This study systematically evaluated the pharmacological safety and anti-inflammatory efficacy of E. racemosa extracts, with concurrent identification and characterization of their primary bioactive components. METHODS: The chemical composition of E. racemosa extract (ERE) was analyzed using HPLC and LC-MS techniques. The safety and in vivo anti-inflammatory effects of ERE were evaluated using the maximum tolerated dose (MTD) in ICR mice and a dextran sodium sulfate-induced ulcerative colitis model in C57BL/6 J mice. RESULTS: HPLC and LC-MS analyses revealed that ERE contained abundant flavonoid active ingredients. MTD study confirmed that ERE exhibited good safety. The symptoms of persistent weight loss, DAI, and shortened colon length in UC mice were suppressed by ERE. Pathological damage in colon tissues was attenuated by ERE, with a considerable reduction in histopathological scores and a substantial increase in the number of goblet cells. The levels of IL-6, IL-1beta, and TNF-alpha in serum were significantly decreased following ERE treatment. Moreover, nitric oxide (NO) levels and myeloperoxidase (MPO) activity in colon tissues decreased, whereas glutathione (GSH) levels and superoxide dismutase (SOD) activity in colon tissues increased after ERE treatment. Furthermore, ERE could regulate the intestinal microbial composition and maintain intestinal flora homeostasis, thereby inhibiting inflammatory responses. CONCLUSION: ERE exhibited a favorable safety profile and alleviated UC through multiple mechanisms. It is expected to serve as a promising low-toxicity natural product for adjuvant treatment in UC.