Objective: To predict and explore the target and mechanism of Huangqi Guizhi Wuwutang in the treatment of diabetic peripheral neuropathy (DPN) through systemic pharmacology. Method: The active constituents and related target proteins of Huangqi Guizhi Wuwutang were searched through TCMSP database. Cytoscape 3.5.1 was used to construct the topology analysis for the active ingredient-target interaction network of Huangqi Guizhi Wuwutang; STRING online database was used for the protein-protein interaction (PPI) network construction and analysis; target protein gene name was obtained from Uniprot database

David database was used for the analysis of KEGG pathway enrichment and the study for the mechanism and targets of Huangqi Guizhi Wuwutang in Treating DPN. Result: Quercetin

kaempferol

beta-sitosterol

7-O-methylisomucronulatol and isorhamnetin were the core compounds of Huangqi Guizhi Wuwutang. The core targets included Prostaglandin G/H synthase 2

Heat shock protein HSP 90

Nuclear receptor coactivator 2; PPI network diagram showed that the key components of the active ingredients of Huangqi Guizhi Wuwutang mainly included JUN

Tumor protein p53(TP53)

c-fos(FOS)

mitogenactivated protein kinase 1(MAPK1)

transcription factor p65(RELA)

interleukin-8(IL-8); KEGG results showed that the main effects of Huangqi Guizhi Wuwutang were correlated with TNF signaling pathway

Toll-like receptor signaling pathway and other signaling pathways. Conclusion: Huangqi Guizhi Wuwutang can exert the efficacy through a variety of channels

with multiple signaling pathways acting on a variety of targets. It can be effectively predicted and analyzed by systematic pharmacology through a variety of databases and statistical analysis software

so as to show its potential effect and mechanism of action.