Epigenetic regulation involves heritable changes in gene expression that do not alter the underlying DNA sequence. The importance of epigenetics in the pathogenesis of various diseases has become increasingly apparent, as it regulates crucial processes such as cell differentiation, proliferation, and apoptosis. This systematic review aims to comprehensively explore the mechanisms of epigenetic regulation, its role in disease, emerging biomarkers for disease detection, and potential therapeutic strategies targeting epigenetic alterations. Mechanisms like DNA methylation, histone modifications, non-coding RNA regulation, and chromatin remodeling contribute to the onset and progression of cancers, cardiovascular diseases, neurodegenerative disorders, and metabolic conditions. Recent advances in epigenetic therapies, such as DNA methylation inhibitors, histone deacetylase inhibitors, and gene editing technologies, hold great promise for therapeutic intervention. This review discusses these developments in detail and explores how epigenetic therapies can be integrated into personalized medicine.