<p>The epigenome, representing the comprehensive landscape of epigenetic modifications within an organism, plays a pivotal role alongside the genome in regulating development, cellular function, and disease susceptibility. Among these modifications, DNA methylation is a central and dynamic mechanism that regulates gene expression without altering the underlying genetic sequence. Increasing evidence highlights the significant influence of dietary bioactive compounds, such as resveratrol, catechins, quercetin, vitamins, and amino acids on epigenetic regulation. Through the intervention of DNA methylation, bioactive substances are involved in the regulation of immunity, lipid metabolism, antioxidant damage, and anti-tumor, which represents a new mechanism by which bioactive substances play various functions. This review explores the epigenetic properties of dietary active substances and emphasizes their role in mediating DNA methylation providing deeper insights into their mechanisms of action and potential health benefits.</p> Graphical abstract <p></p>