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Mangroves are valuable reservoirs of diverse phytochemicals with significant therapeutic potential. Beyond their ecological roles, these bioactive compounds can influence epigenetic mechanisms, heritable changes in gene expression without alterations in the DNA sequence itself, which are now widely implicated in the development and progression of various non-communicable diseases (NCDs). This review evaluates the epigenetic-targeting potential of key mangrove-derived phytochemicals, focusing on their mechanisms. Reported effects include the modulation of dysregulated signalling pathways in carcinogenesis, reduction of inflammation, alleviation of heavy metal toxicity, and anti-viral, anti-adipogenic, and anti-allergic actions. Furthermore, these compounds show promise in chemoprevention, protection of pancreatic β-cells in diabetes, treatment of endometriosis, and mitigation of sepsis-induced intestinal damage. This article aims to encourage pharmacognosists, marine biologists,traditional health professionals, and biochemists to pursue deeper investigations into the synthesis, mechanisms, and applications of these bioactive compounds, a field that remains underexplored in the existing literature.