Objective To explore the multi-scale action mechanism of Scutellaria barbata and Hedyotis diffusa on the treatment of gastric cancer. Methods Firstly, the chemical components of Scutellaria barbata and Hedyotis diffusa were retrieved according to chemical informatics. Then, the active ingredients were screened based on the OB and DL parameters. Subsequently, the targets of active ingredients were fished out using the support vector machines and random forest algorithms. At the same time, employing the molecular docking approach, the active ingredients and corresponding targets were verified and screened. Finally, the effective ingredient-target, effective ingredient-target-functional network is constructed. Results In this study, a total of 35 active ingredients and 64 targets were screened. Among them, the most important targets are androgen receptor (AR), estrogen receptor (ESR1), carbonic anhydrase 2 (CA2), non-receptor protein tyrosine phosphatase 1 (PTPN1), serine/threonine acid protein kinase (PIM1) and cell division protein kinase 2 (CDK2). The results of biological function enrichment analysis showed that these targets mainly act on the four signal pathways including calcium signal, cGMP-PKG, estrogen and cAMP signal pathways. Conclusion The active ingredients of Scutellaria barbata and Hedyotis diffusa formed the interaction network with their protein targets, and then regulated pivotal signal pathways to achieve the purpose of treating gastric cancer. Overall, this study reflects the multi-scale mechanism of traditional Chinese medicine with the character of multi-component, multi-target and multi-pathway in the treatment of tumors, providing a new idea for the clinical treatment of gastric cancer, and also a new method for the innovation and development of traditional Chinese medicine.