Ethnopharmacological relevance: Paris polyphylla Sm. (P.P), is a widely-used traditional Chinese medicine (TCM) in the treatment of wound, throat sores and snakebites. Furthermore, P.P was recorded as an anti-inflammatory drug by the Chinese Pharmacopoeia.Aim of the study: We sought to decipher the anti-inflammatory effect of P.P on ulcerative colitis (UC); specifically, to explore whether P.P attenuates colitis by restoring the regulatory T cells (Tregs) and T helper 17 (Th17) cells balance and its mechanism.Material and methods: We treated experimental colitis mice with extracts of Paris polyphylla (EPP). The percentage of Tregs and Th17 cells were measured using flow cytometry, and their secreted cytokines levels were evaluated employing ELISA. The expression of peroxisome proliferator-activated receptor gamma (PPAR-?) in colon tissues was detected using immunofluorescence. Furthermore, GW9662, a PPAR-? antagonist, was used to validate the mechanism of EPP in restoring the Treg/Th17 balance.Results: The EPP effectively alleviated the clinical symptoms and inflammatory cytokine levels in mice with colitis. EPP treatment also restored the impaired Treg/Th17 balance in mice. Furthermore, EPP treatment pro-moted PPAR-? expression and reduced HIF-1a and p-STAT3 expression in colon tissues, whereas PPAR-? inhi-bition blocked the effects of EPP in mice models.Conclusion: Our study indicates that EPP exhibit excellent anti-inflammatory properties via restoring PPAR-?/STAT3/HIF-1a axis-mediated Treg/Th17 balance in colitis mice. Hence, P. polyphylla is a promising medicinal plant-based alternative for managing colitis that requires further clinical validation.