Objective To investigate the efffcacy and potential mechanism of Hedyotis diffusa Willd. in delaying skin photoaging by combining network pharmacology and molecular docking. Methods The active ingredients of Hedyotis diffusa Willd. were obtained from TCMSP, HERB, and TCM-ID databases, and its potential targets were screened out. The disease-related targets of skin photoaging were retrieved and screened through GEO and GeneCards databases. The intersection targets of Hedyotis diffusa Willd. and skin photoaging were imported into the STRING database to construct a PPI network. Visualization and topological analysis were performed using Cytoscape 3.9.0 to screen the key targets of Hedyotis diffusa Willd. in intervening skin photoaging. Furthermore, the key targets were imported into the DAVID database for GO function and KEGG pathway enrichment analysis. Molecular docking (AutoDock Vina 1.1.2) and molecular dynamics simulation (Gromacs 2022.3 software) were conducted for key components and targets. Results A total of 37 active ingredients of Hedyotis diffusa Willd. and 970 potential targets of skin photoaging were obtained. After screening and deduplication, 41 intersection targets of the drug and the disease were identiffed. The results of GO and KEGG enrichment analysis showed that Hedyotis diffusa Willd. was related to biological processes such as collagen catabolic process and cellular response to lipopolysaccharide, and its mechanism was to regulate IL-17 signaling pathway, TNF signaling pathway, etc. Molecular docking results showed that the binding energies of the active ingredients of Hedyotis diffusa Willd. to the core targets were all less than -5 kcal/mol. Molecular dynamics simulation results showed that the complexes of PTGS2 and MMP9 bound to quercetin had stable conformations. Conclusion Active ingredients such as colchicine, ursolic acid, and quercetin in Hedyotis diffusa Willd. may exert the effect of delaying skin photoaging by regulating signaling pathways such as IL-17 and TNF, and acting on targets such as MMP9 and PTGS2.