To explore the active components and medication rules of Chinese medicines in regulating DNA methylation.Methods:GeneCards was used to search for the gene targets related to DNA methylation,and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) to search for the active ingredients and herbal medicines related to the target genes.The inclusion conditions were drug-likeness≥0.18 and oral bioavailability≥30%,and the herbal medicine-component-target network was constructed.DAVID 6.8 was used to analyze the biological processes and signaling pathways involving the potential targets.At the same time,the efficacy,property,taste,and meridian tropism of the Chinese herbal medicines were collected to analyze the medication rules for regulating DNA methylation.Results:Twenty-three potential targets of DNA methylation were obtained,which were matched with 449 active components and 342 Chinese herbal medicines.Quercetin,kaempferol,luteolin,baicalin,and isorhamnetin may be the main active components for interfering with DNA methylation.Glycyrrhizae Radix et Rhizoma,Scutellariae Barbatae Herba,Salviae Miltiorrhizae Radix et Rhizoma,Lycii Fructus,and Erigerontis Herba may be the main Chinese herbal medicines for interfering with DNA methylation.The anti-inflammatory pathways such as TNF and Toll-like signaling pathway were mainly involved.The Chinese herbal medicines used for interfering with DNA methylation are cold and bitter,with tropism to the liver meridian and the main effects of clearing heat,relieving pain,and tonifying.Conclusion:This study predicted the active components of Chinese herbal medicines in regulating DNA methylation and summarized the medication rules for intervening with DNA methylation.It provides ideas for the experimental verification of treating DNA methylation-related diseases and the development of relevant drugs.