Objective:To explore the mechanism of Gynostemma pentaphyllum in the treatment of atherosclerosis (AS) based on network pharmacology. Methods:TCMSP was used to analyze the chemical components and targeted effect of Gynostemma pentaphyllum, through the database like OMIM, TTD, drugbank and digsee to predict and screen the targeted effect of AS. The genes corresponding to the target were queried by UniProt database, and then the compound target (gene) network and protein-protein interaction network (PPI) were constructed by using Cytoscape 3.2.1 to screen out the core target. Finally, the function enrichment analysis of Gene Ontology (GO) and the pathway enrichment analysis based on Kyoto Encyclopedia of genes and genomes (KEGG) were carried out by David, and the mechanism of action was studied. Results:The compound-target network consisted of 13 compounds and 150 corresponding targets. The key targets were PGR, NR3C2, NCOA2, PPARG, PTGS1, PTGS2, etc. PPI network contains 131 proteins and 46 core proteins. There are 480 GO item in GO function enrichment analysis, including 403 entries in biological process (BP), 35 entries in cell composition (CC), and 42 entries in molecular function (MF). 25 signaling pathways related to AS were obtained by enrichment and screening of KEGG pathway, involving PI3K-AKT, TNF, HIF-1, MAPK, toll like receptor and other signaling pathways.Conclusions:This paper discussed the mechanism of Gynostemma pentaphyllum in the treatment of AS through network pharmacology, which provides new ideas and methods for further research and exploration of the mechanism of Gynostemma pentaphyllum in the treatment of AS.