Aim. Ulcerative colitis (UC) is a refractory gastrointestinal disease. The study aimed to expound the mechanism of Polygonum bistorta (PB) in treating UC by network pharmacology, molecular docking, and experiment verification. Methods. The compositions and targets of PB and UC-associated targets were obtained by searching the websites and the literature. The potential mechanism of PB in the treatment of UC was predicted by protein-protein interaction network construction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Molecule docking was performed by AutoDock. In vitro experiments explored the mechanism of quercetin (Que), the main active composition of PB, in treating UC. Results. Six compositions, 139 PB targets, and 934 UC-associated targets were obtained. 93 overlapping targets between PB and UC were identified, and 18 of them were the core targets. 467 biological processes, 10 cell components, and 30 molecular functions were obtained by GO analysis. 102 pathways were enriched through KEGG analysis. Among them, the IL-17 signaling pathway had high importance. The core targets FOS, JUN, IL-1β, CCL2, CXCL8, and MMP9 could dock with Que successfully. Act1, TRAF6, FOS, and JUN were identified by KEGG as the key proteins of the IL-17 signaling pathway. The expressions of the abovementioned proteins were increased in Caco-2 cells stimulated by Dextran sulfate sodium and decreased after being treated by Que. Conclusion. PB might treat UC by downregulating the IL-17 signaling pathway. It is worth doing further research on PB treating UC in vivo.