Abstract: Objective: To study the molecular mechanism of Phedimus aizoon (Linnaeus)'t Hart. on anti-inflammatory effect by network pharmacology, molecular docking, and experiment research. Methods: The potential anti-inflammatory effect ingredients and targets were acquired from TCMSP, HERB, and other databases under the screening condition of oral bioavailability ≥30%. The inflammation-related targets were collected from GeneCards, OMIM, and other databases, and the protein-protein interaction (PPI) analysis to obtain the key anti-inflammatory effect targets. Meanwhile, GO annotation and KEGG signal pathway enrichment analysis of the key targets was analyzed using the David database. Moreover, this study verified the key targets predicted by AutoDock molecular docking. The key anti-inflammatory effect ingredients of Phedimus aizoon (Linnaeus)'t Hart. were analyzed using high-performance liquid chromatography (HPLC). The anti-inflammatory effect of the key ingredients was verified on the LPS-induced RAW264.7 cell model. Results: The results showed that there were five potent components corresponding to 130 related targets, and 421 inflammation-related targets, with 22 intersection anti-inflammatory targets, among which the key targets were PPARG, EGFR, TP53, etc. β-sitosterol and gallic acid (3,4,5-trihydroxy benzoic acid) were the main ingredients that can be anti-inflammatory. GO annotation and KEGG signal pathway enrichment analysis indicated that β-sitosterol and gallic acid played an anti-inflammatory role through multiple pathways such as transcription from RNA polymerase II promoter, positive regulation of neuron apoptotic process, and response to lipopolysaccharide, etc., as well as signal pathways including pathways in cancer, hepatitis B, TNF signaling pathway, MAPK signaling pathway, and other signaling pathways. Furthermore, the molecular docking analysis revealed that the key targets had good binding affinities with the key active ingredients. β-sitosterol and gallic acid as active ingredients in Phedimus aizoon (Linnaeus)'t Hart. were analyzed by HPLC. The experimental results showed that β-sitosterol and gallic acid could significantly reduce NO content, increase the content of IL-10 (P<0.05), and play an anti-inflammatory effect. Conclusion: This study revealed that Sedum aizoon L. would play an anti-inflammatory role by regulating multiple targets and multiple pathways, which laid a foundation for the research and application of Phedimus aizoon (Linnaeus)'t, Hart.