Background: Jiawei Ling Gui Zhu Gan Decoction (JW-LZD) is based on Linggui Zhugan Decoction (LZD) and adds eight traditional Chinese medicines: Codonopsis pilosula, Astragalus membranaceus, Yam, Epimedium, Morinda officinalis, Tangerine Peel, Pinellia ternata and Coix Seed, which can be used for the treatment of obesity in the clinical. However, the pharmacological mechanisms of JW-LZD remain unclear. Methods: In this study, we determined the molecular targets and mechanismsinvolved in obesity treatment through network pharmacological analysis, andmolecular docking technology. Related compounds were obtained from the TCMSP.Oral bioavailability and drug-likeness were screened using pharmacokinetic criteria.Molecular targets were identified in the drug-bank database and compared withobesity disease differential genes with P < 0.05 and ∣ log2FC > 0.5 obtained in theGEO-database to obtain cross genes and construct the TCM compound diseaseregulation network. After constructing PPI, Go, and KEGG analyses, the key activecomponents and target genes were selected. Molecular docking was carried out usingAutoDock, and the best binding target was selected to select the best binding targetfor molecular docking.Results: A total of 248 potential compounds and 30 strongly associated JW-LZDtargets were identified. Pathway enrichment analysis showed that putative JW-LZDtargets mostly participated in adenylate cyclase-activating adrenergic receptorsignaling, adrenergic receptor signaling, regulation of signal receptor activity,coagulation, and other metabolic related biological processes. The molecular dockingresults showed that the key JW-LZD components have good potential to combine withthe target genes ADRB2, ADRA2A, ADRA2C, CHEK1, CHEK2, and DGAT2.Conclusion: JW-LZD could prevent obesity through the molecular mechanisms predicted by network pharmacology, providing a way to develop new combination medicines for obesity.