Objective To screen and validate the traditional Chinese medicine (TCM) monomer that may regulate adipocyte function and improve obesity. Methods Data sets GSE70353 and GSE72158 were downloaded from Gene Expression Omnibus(GEO) database. The former contains 770 men (45-73 years old) with different BMI corresponding gene expression in subcutaneous white adipose tissue (SAT), and the latter contains 42 women (before and 1 year after bariatric surgery) corresponding SAT. The differentially expressed genes (DEGs) of data sets GSE70353 and GSE72158 in GEO were analyzed with R language, and the co-expressed DEGs of the two data sets were screened. Functional annotation Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of co-expressed DEGs were conducted by R language,protein-protein interaction (PPI) network construction and the hub genes screening were completed by STRING database and Cytoscape software. Connectivity map (cMAP) was used to screen the TCMs that can regulate the hub gene. The bergenin (0, 0.4, 2,10 μmol/L) and ginkgolide A (0, 0.01, 0.1, 1 μmol/L) were selected to treat mature white adipocytes (WAT) induced by 3T3-L1 cells for 24 h. The mRNA levels of interleukin-6 (IL-6) and peroxisome proliferator-activated receptor γ (PPARγ) were detected by qRT-PCR. Results There were 64 co-expressed DEGs in the two data sets, GO and KEGG analysis showed that DEGs were enriched in immune cell chemotaxis, complement-related cascade activation, and various inflammatory signaling pathway, responding to nutrient and lipid protein. The 18 hub genes [APOB (up-regulated), ACP5, C1QB, C1QC, CCL2, CCND1, CD163, CD68, FCER1G, ITGB2,MMP9, MS4A6A, MS4A7, PLEK, SPP1, TNFRSF11B, TYROBP, VSIG4 (down-regulated)] were identified by Cytoscape. Twenty-eight TCMs that could regulate hub genes were screened by cMAP, and 22 of them showed the ability of improving obesity. Compared with the control group, the mRNA level of PPARγ decreased in 0.4 μmol/L bergenin group and 0.1 μmol/L ginkgolide A group(P<0.05), and IL-6 mRNA levels decreased in 0.4 μmol/L bergenin group, 10 μmol/L bergenin group and 0.1 μmol/L ginkgolide A group (P<0.05). Conclusion A total of 28 TCMs were screened, of which 22 TCMs have been proved to be able to improve obesity.It has been initially confirmed in present study that bergenin and ginkgolide A could regulate the function of adipocyte.