Abstract: To identify the composition of iridoids from Hedyotis diffusa Willd and explore the mechanism on its anti-renal fibrosis effect based on network pharmacology, LC-Q/TOF-MS (liquid chromatograpy-quadrupole/time of flight mass spectrometry) was used to analyze the iridoid ingredients and the related targets of renal fibrosis were obtained by DisGeNET database and MalaCards database. The potential targets were screened by SYBYL-X7.3 software. We then imported the identified ingredients and potential target genes into Cytoscape3.7.1 to construct the compound-target network and the protein-protein interaction (PPI) network. Finally, the gene ontology (GO) functional enrichment analysis and KEGG pathway enrichment analysis of the selected core genes were made to explore the mechanism of iridoids against renal fibrosis. There were 10 active iridoid compounds and 111 corresponding targets including dimethylarginine dimethylaminohydrolase 1 (DDAH1), heparanase (HPSE), human kirsten rat sarcoma viral oncogene (KRAS), moesin (MSN), etc. in compound-target network. The GO functional enrichment analysis obtained 211 GO entries. Twenty related signal pathways including Toll-like receptor signaling pathway, transforming growth factor-beta (TGF-β) signaling pathway, renal cell carcinoma signaling pathway, and the Janus kinase/signal transducer and activator of tran-ions (Jak-STAT) signaling pathway were selected by KEGG enrichment analysis. We preliminarily investigated the mechanism of the iridoid compounds on renal fibrosis to provide guide information for the subsequent experimental research and clinical application.