Objective To investigate the effect of Hedyotis diffusa on skin photoaging and its possible mechanism through the combination of network pharmacology and molecular docking. Methods The active ingredients of Hedyotis diffusa were obtained from TCMSP, HERB and TCM-ID databases, and the potential targets of Hedyotis diffusa were screened. The disease-related targets of skin photoaging were obtained from GEO and GeneCards databases. The intersection targets of Hedyotis diffusa and skin photoaging were introduced into the String database for PPI analysis, and Cytoscape3.9.0 visualization and topology analysis were used to obtain the key targets of hedyotis diffusa in the treatment of skin photoaging. The key targets were imported into the DAVID database to obtain the GO and KEGG enrichment analysis results, and molecular docking and molecular dynamics simulation were performed for the key components and targets. Results A total of 41 intersection targets of drugs and diseases were obtained after screening and de-duplication. The results of GO and KEGG enrichment analysis showed that Hedyotis diffusa was related to biological processes such as collagen catabolism and cellular response to lipopolysaccharide, and the mechanism was the regulation of IL-17 signaling pathway and TNF signaling pathway. Molecular docking results showed that the binding energies of the active components of Hedtis diffusa to their core targets were less than -5 kcal/mol. Molecular dynamics simulation results showed that the complex of PTGS2 and MMP9 with quercetin had a stable conformation. Conclusions Colcemid, ursolic acid, quercetin and other active ingredients from Hysophidium papyraceae may play a role in delaying skin photoaging by regulating IL-17, TNF signaling pathway and acting on MMP9, PTGS2 and other targets.