Inflammatory bowel disease (IBD) is a chronic, recurrent, and remitting inflammatory disease with unclear etiology. As a clinically frequent disease, it can affect individuals throughout their lives, with multiple complications. Unfortunately, traditional murine models are not efficient for the further study of IBD. The zebrafish model has been used to study the composition of intestinal microbiota, novel genes, and therapeutic approaches. The pathogenesis of IBD is still unclear and many risk factors remain unidentified. Conventional treatment of ulcerative colitis is accompanied by a certain number of adverse effects. The use of herbal therapy in inflammatory bowel disease (IBD) is increasing worldwide. The present study was to evaluate the antioxidant activity using DPPH assay and anti-ulcerative colitis of polyherbal extract (Curcuma longa, Andrographis paniculate, Cynodon dactylon and Citrus limon) in DSS (Dextran sodium sulphate) induced Zebrafish model. 0.25% DSS given to the zebrafish for 7 days. On 8 th day given for histopathological examination. The phytoconstituents present in the polyherbal extract was confirmed by FTIR and HPTLC. Presence of Phytoconstituents Flavonoids, Tannins, Triterpenoids exhibits a substantial reduction of internal inflammation and reduce intestinal mucosa damage. Herbal therapies exert their therapeutic benefit by different mechanisms including immune regulation, antioxidant activity