Objective To explore the molecular mechanism of the active compounds in Shuangjiang Weitong Pill in the treatment of gastritis. Methods Traditional Chinese Medicine Systemic Pharmacology Analysis Platform (TCMSP), High-Throughput Experimental and Reference Database for Traditional Chinese Medicines (HERB), Public Chemical Database (PubChem), Online prediction platform for drug-induced pharmaco-genicity and toxicity indicators (ADMET lab2.0), Online prediction platform for compound-related targets (Swiss Target Prediction) were used obtained active compounds and targets. Gastritis targets were extracted by using the human gene database (GeneCards) and the human online Mendelian genetic database (OMIM). The intersection target and compound-target-disease network were obtained through Venn diagram and Cytoscape3.9.1. The core compounds were determined according to the Degree value. Protein interaction network (PPI) was from STRING. The core targets were determined according to the Degree value. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genes (KEGG) enrichment analysis were performed on the core targets and the core signaling pathway was obtained. Finally, molecular docking and molecular dynamics simulations were used to verify the binding of core targets and components. Results The results of network pharmacological analysis showed that the 22 core components in Shuangjiang Weitong Pill may play a role in the treatment of gastritis by regulating 16 core targets. The epidermal growth factor receptor (EGFR) signaling pathway was the core pathway of Shuangjiang Weitong Pill in the treatment of gastritis. The molecular docking results confirmed the strong binding between the core components and the key targets in the EGFR signaling pathway, EGFR, GSK3B, JAK1 and SRC. The binding energies of Desglucoanagalloside B (DBR12), Methyl lucidenate F (KCZ14) and Cyqualon (JH14) to EGFR were -10, -9.3 and -9.1 kcal/mol, respectively, and the binding degree was better than that of EGFR eutectic ligands. Molecular dynamics simulations verified EGFR formed stable and strong binding to DBR12, KCZ14 and JH14 and the average binding free energies calculated by the molecular mechanics/generalized Born surface area (MM/GBSA) method were -39.28, -23.19 and -42.03 kcal/mol, respectively. Conclusion Shuangjiang Weitong Pill had the characteristics of multi-component, multi-target and multi-signaling pathway synergy in the treatment of gastritis. EGFR, Glycogen synthase kinase 3β (GSK3B), Janus kinase 1 (JAK1) and Tyrosine protein kinase-SRC (SRC) may be the key targets, and the EGFR signaling pathway was the core signaling pathway. This can provide a scientific basis for further research on the mechanism of action of Shuangjiang Weitong Pill in the treatment of gastritis.