This review integrates evidences from multi-database (PubMed, Web of Science and CNKI, 2010–2025) to elucidate three core epigenetic mechanisms of plant polysaccharides (e.g., Astragalus and Ganoderma lucidum): 1) TET2-mediated DNA demethylation; 2) inhibition of histone-modifying enzymes including JMJD2D; 3) regulation of tumor-suppressive miRNAs such as miR-139-5p. The gene discussed is KDM4D; the disease is neoplasm.