This study used a network pharmacology approach to investigate the potential active ingredients of Sini Powder and Tong xie yao fang decoction and the underlying mechanisms in irritable bowel syndrome (IBS) treatment. The potential active ingredients of Sini Powder and Tong xie yao fang decoction were obtained from TCMSP databases, and the potential targets of the active ingredients were predicted and analyzed by using the Swiss Target Prediction database. T Genecard, DisGeNET, and OMIM databases were processed to screen the potential therapeutic targets in IBS. The interaction of overlapped candidates between the potential biotarget of herb extracts and the potential therapeutic target of IBS were analyzed by STRING website and visualized by the Cytoscape V3.8.0 software. Gene ontology (GO) analysis and Kyoto Genomics and Genomics Encyclopedia (KEGG) pathway were processed to categorize and map the potential biofunctions and effects of these candidates by using David database. Result. There were 139 predicted active components and 248 related biotargets of Sini Powder and Tong xie yao fang decoction which were involved in IBS treatment, and 522 annotations and 101 related pathways are obtained by enrichment analysis (P < 0.01, FDR < 0.05). The underlying mechanisms of Sini Powder and Tong xie yao fang decoction may be related to neuroactive ligand-receptor interaction, calcium, cAMP, and HIF-1 signaling pathways. In conclusion, our results showed that the effect and mechanism of Sini Powder and Tong xie yao fang decoction in IBS treatment were in multi-ingredient, multitargets and multipathways, which would provide several potential and promising strategies for the further research and development of Sini Powder and Tong xie yao fang decoction on IBS treatment.Copyright © 2022 Rong Tang et al.