Abstract: Objective: The network pharmacology method was used to explore the mechanism of Sanpian Decoction (SPD) in the treatment of migraine. Methods: TCMSP database was used to collect the main components of drugs in SPD. At the same time, ADME screening was carried out to obtain the potential active components. Meanwhile, SwissTargetPrediction was used to obtain the function targets of active components. OMIM database and GeneCards database were used to collect migraine-related targets, and importing the screened drug targets and disease targets into the jvenn website to acquire common targets. The PPI network of common targets was constructed by using STRING database, and the “drug target disease” network diagram was constructed by using Cytoscape 3.7.2 software. Then the network was analyzed. The common targets were imported into Metascape database in order to analyze the GO enrichment and KEGG pathway enrichment. Results: There were 205 common targets by filtering and 25 key genes were identified by PPI analysis. The “drug-target-disease” network contains 157 compounds and 205 targets. 256 signaling pathways were gained by KEGG pathway enrichment. GO enrichment analysis showed 550 GO items (p<0.01), which includes 306 biological process items, 108 cell component items, and 136 molecular function items. Conclusion: The potential active components of SPD for the treatment of migraine may be Kaempferol, Rotundine and Heraclenin, which are closely related to genes such as APP, CCR5, OPRK1, CXCL8. SPD may play a therapeutic role in migraine by regulating MAPK signaling pathway, PI3K-Akt signaling pathway, and HIF-1 signaling pathway.