Objective To explore the potential molecular mechanism of Maitong Jun’an decoction (MTJA) in the treatment of coronary heart disease based on network pharmacology, molecular docking and animal experiments. Methods The main active components and corresponding protein targets of MTJA were screened in Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissTargetPrediction combined with literatures. Genes associated with myocardial infarction and heart failure in coronary heart disease were searched in DisGeNET, Genecards and Online Mendelian Inheritance in Man (OMIM) databases. The intersection of compound targets and disease targets was obtained, and “medicine-composition-target-disease” network was constructed. The overlapping targets were imported into STRING database to construct protein-protein interaction (PPI) network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the targets, and molecular docking studies were further conducted on the core targets and active compounds. The rat model of myocardial infarction was established. The morphological and pathological changes of heart tissue were observed by hematoxylin-eosin staining, and the expression of core target protein was detected by Western blotting. Results There were 264 nodes and 1 193 interrelationships in the “medicine-composition-target-disease” network. Quercetin and kaempferol were the key components as ranked by degree value. The proteins with high degree in PPI network were interleukin (IL)-6, IL-1β and protein kinase B 1 (Akt1). GO and KEGG analyses showed that the mechanism of MTJA in the treatment of coronary heart disease mainly involved lipids and atherosclerosis, advanced glycation end product (AGE)-receptor for advanced glycation end product (RAGE) signaling pathway in diabetes complications, fluid shear stress and atherosclerosis, IL-17 signaling pathway, etc. The results of molecular docking showed that the important compounds of MTJA had strong binding ability with the core target. The results of animal experiments showed that MTJA could significantly alleviate the myocardial injury in rats with myocardial infarction, and reduce the expression levels of IL-1β and IL-6 proteins in apical tissue of rats with coronary heart disease. Conclusion MTJA may play a role in the treatment of coronary heart disease by reducing the expression levels of IL-1β and IL-6 proteins.