To explore the mechanism of Yangxinshi Tablet(YXS) in the treatment of coronary heart disease(CHD) complicated with major depressive disorder(MDD) by network pharmacology and molecular docking technology. TCMSP and TCM-ID databases were used to screen the active components and related targets of YXS, and Uniport database was used to retrieve the standard gene names of targets. GeneCards and OMIM databases were used to collect the disease targets of CHD and MDD. The drug and disease intersection targets were imported into STRING platform to obtain protein interactions, gene ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analysis were performed using David database. AutodockTools software was used for molecular docking verification. Enrichment analysis shows that YXS acts on signal transducer and activator of transcription-3, interleukin 1-β, interleukin-6 and other 290 targets through 295 active components such as quercetin, luteolin, kaempferol and soya-lecithin, involving AGE-RAGE, lipid and atherosclerosis, fluid shear stress and atherosclerosis and other signaling pathways. Molecular docking shows good docking. YXS intervenes in CHD complicated with MDD through multi-components, multi-targets and multi-pathways, providing a theoretical basis for subsequent experimental research and clinical drug use.