Abstract： Objective： Based on the theory of "homotherapy for heteropathy" in traditional Chinese medicine （TCM） and network pharmacology，this study aims to analyze the mechanism of action and the material basis of the pharmacodynamic effects of Sini Powder in the treatment of metabolic-associated fatty liver disease （MAFLD） and irritable bowel syndrome （IBS）. Methods： The active ingredients and targets of the drugs were screened based on databases such as Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. Disease targets for MAFLD and IBS were obtained from databases such as GeneCards. Cytoscape 3.9.1 software was used to construct a "drug-active ingredient-common target-disease" network， and degree values were calculated to screen the main active ingredients. The Venny platform was used to obtain the intersection targets of the drugs and the diseases， which were then imported into the STRING database to construct a protein-protein interaction （PPI） network and identify core therapeutic targets. The DAVID platform was utilized for Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses of the core targets. Molecular docking verification between the main active ingredients and the core therapeutic targets was performed using AutoDockTools software. Results：A total of 37 intersection targets of Sini Powder for treating MAFLD and IBS were identified. Main active ingredients， including luteolin， quercetin， and kaempferol， and core targets， including tumor necrosis factor（TNF）， interleukin （IL）-6，IL-1β and AKT serine/threonine kinases 1 （AKT1） were screened and determined. GO functional enrichment analysis yielded 347 biological processes， 24 cellular components， and 206 molecular functions， indicating that Sini Powder treatment for MAFLD and IBS involves the regulation of vascular endothelial growth factor， miRNA transcription，and smooth muscle cell proliferation. KEGG pathway enrichment analysis identified 110 pathways， primarily related to glucose and lipid metabolism pathways， pathways in cancer， and oxidative stress pathways. Molecular docking showed that the binding energies between the main active ingredients and the core targets were all less than -5 kcal/mol. Conclusion： The core active ingredients in Sini Powder， such as luteolin， quercetin， and kaempferol，act on core therapeutic targets such as TNF，IL-6，IL-1β，and AKT and regulates signaling pathways related to glucose and lipid metabolism，cancer，and oxidative stress，thereby exerting the effect of "homotherapy for heteropathy" for both MAFLD and IBS.