Abstract： Objective： To analyze the mechanism of Jianpi Yishen Prescription combined with Tripterygium Glycosides Tablets in treating immunoglobulin A nephropathy （IgAN） using network pharmacology and molecular docking technology combined with GEO dataset machine learning methods. Methods： The active ingredients and corresponding targets of Jianpi Yishen Prescription and Tripterygium Glycosides Tablets were screened through TCMSP and UniProt. IgAN-related targets were retrieved from GeneCards， OMIM， TTD， DrugBank， DisGeNET， and Ensembl databases. The Venn online tool was used to obtain intersecting targets between drugs and disease. Based on protein-protein interaction （PPI） information from the STRING database， a PPI network was constructed using Cytoscape visualization tools to screen core targets. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using Metascape. In R software，the Least Absolute Shrinkage and Selection Operator （LASSO），Random Forest （RF），and Support Vector Machine-Recursive Feature Elimination （SVM-RFE） algorithms were used to evaluate the identification ability of core targets for case and control groups in the GSE93798 dataset to determine key genes. Cytoscape was employed to construct a network and screen main active ingredients. Molecular docking validation was then performed. Results： The main active ingredients of Jianpi Yishen Prescription combined with Tripterygium Glycosides Tablets in treating IgAN included quercetin， kaempferol， luteolin， β-sitosterol， and formononetin. There were 12 core targets， including interleukin-6 （IL-6），B-cell lymphoma 2 （BCL2），and tumor protein p53 （TP53）. Two key genes were screened out by machine learning： FBJ murine osteosarcoma viral oncogene homolog （FOS） and avian sarcoma virus 17 oncogene homolog （JUN）. GO enrichment analysis showed that biological processes （BP） mainly involved positive regulation of cell migration and cellular response to lipids；cellular components （CC） mainly involved the external side of the plasma membrane， membrane rafts， and vesicle lumen； molecular functions （MF） mainly involved transcription factor binding and protein kinase binding. KEGG pathways primarily involved pathways in cancer and the advanced glycation end products-receptor for AGE （AGE-RAGE） signaling pathway in diabetic complications. Molecular docking results demonstrated stable binding forces between core targets and main active ingredients. Conclusion： Jianpi Yishen Prescription combined with Tripterygium Glycosides Tablets may act on core targets such as FOS and JUN to regulate cell proliferation and inflammatory responses，exerting antioxidant and anti-fibrotic effects in treating IgAN.