<p>Autoimmune diseases are chronic disorders characterized by dysregulated immune responses directed against self-tissues. However, current therapies are limited by suboptimal efficacy, substantial adverse effects, or an inability to halt or reverse disease progression. Emerging evidence indicates that epigenetic regulation—including DNA methylation, histone modification and non-coding RNA—has a central role in the pathogenesis of autoimmune diseases, creating transformative opportunities for the development of targeted therapies. This review provides an up-to-date synthesis of advances in epigenetic drugs for major autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis, and examines the molecular mechanisms through which these agents modulate immune cell differentiation and function. Accumulating data from preclinical models and clinical studies suggest that epigenetic therapies not only suppress inflammation but also reprogramme aberrant immune states, conferring therapeutic potential for disease amelioration. At present, twelve epigenetic drugs have been approved for cancer, and given the shared epigenetic abnormalities between cancer and autoimmune diseases, extending these therapeutic indications to autoimmune disorders represents a feasible strategy. Moreover, combination regimens incorporating epigenetic drugs have demonstrated enhanced therapeutic efficacy. These findings highlight opportunities for drug repurposing and translational innovation. Despite challenges related to specificity and safety, epigenetic therapies are poised to drive a paradigm shift in the treatment of autoimmune diseases, and future studies integrating epigenomic profiling with precision medicine will be essential to enable their personalised clinical application.</p>