Aim To explore the mechanism of action of Sanleng-Ezhu herbal pair in the treatment of atherosclerosis (As) by using network pharmacology and molecular docking technology. Methods The relationship between related therapeutic targets was discovered and explored through TCMSP, Swiss Target Prediction, STRING database and Cytoscape software. GO enrichment analysis and KEGG pathway enrichment analysis were performed through the Omicshare platform. Molecular docking was performed by using the DockThor platform. Results 158 related therapeutic targets were found in the research results, including 49 core targets such as serine/threonine protein kinase 1, SRC proto-oncogene, tumor necrosis factor, mitogen-activated protein kinase 3, and interleukin-6. GO enrichment analysis found that the Sanleng-Ezhu herbal pair could affect the occurrence and development of As in many ways. KEGG pathway enrichment analysis found that the Sanleng-Ezhu herbal pair may play a role in the treatment of As through multiple metabolic pathways such as the C-type lectin receptor signaling pathway and the cancer pathway. Molecular docking showed that the binding activity of target TNF with hederagenin was the highest. Conclusion The mechanism of action of Sanleng-Ezhu herbal pair in the treatment of As is complex, and it mainly acts through multiple metabolic pathways such as C-type lectin receptor signaling pathway and cancer pathway.