Objective This study aims to explore the potential mechanism of Datura stramonium in treating psoriasis using network pharmacology.Methods In this study, high-throughput retrieval of active components of Datura metel was first performed based on the Traditional Chinese Medicine Systems Pharmacology Analysis Platform combined with the PubChem chemoinformatics database. Subsequently, the Swiss Target Prediction system was used to conduct target spectrum analysis on candidate active compounds. Simultaneously, psoriasis-related targets were systematically captured through the OMIM disease genomics database and GeneCards gene annotation knowledge base. Finally, the Venny 2.1.0 bioinformatics visualization tool was employed for topological analysis of the drug-disease target network, and core action target groups of Datura metel in treating psoriasis were revealed through multi-dimensional validation mechanisms. The protein-protein interaction (PPI) network was constructed using the STRING database, and the core genes of PPI were screened plugin of Cytoscape software. The "drug-component-target-disease" network diagrams were constructed using Cytoscape software. The DAVID database was used to conduct gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on the above intersection target sites to obtain the biological mechanism of Datura stramonium in treating psoriasis.Results Through database analysis, 310 target sites of Datura stramonium were screened out, 4466 psoriasis-related target sites were obtained, and 224 common target sites were identified. 49 key target sites were screened out from the PPI network. GO functional enrichment analysis shows that the biological processes and functions of Datura metel are concentrated on protein- and adenosine triphosphate (ATP)-related functions, plasma membrane and membrane structures in cellular components, and protein phosphorylation and chromatin remodeling activity in molecular functions, etc. KEGG pathway enrichment showed that the treatment of psoriasis by Datura stramonium mainly involved pathways in cancer, endocrine resistance, AGE-RAGE signaling pathway in diabetic complications, prostate cancer, etc.Conclusion Based on the network pharmacology research method, this study found that the pharmacological basis of Datura stramonium in treating psoriasis lies in its multiple active components that can exert effects through a multi-target and multi-pathway synergistic regulatory network. The research results provide important theoretical support for further in-depth exploration of the mechanism of Datura stramonium in treating psoriasis and its clinical application.