•Epigenetic events have a great potential to provide outstanding information about the exposition of EDCs.•“The sixth base” (5-hmC) is an appealing epigenetic marker for environmental biosensors.•Post translational modifications has been measured via enzyme activity towards drug development and clinical diagnosis.•Personal health outcomes are the result of the interaction between the exposome and the individual genome. The relationship between endocrine system disorders and health risks due to chemical environmental compounds has become a growing concern in recent years. Involuntary exposure to endocrine disruptors (EDCs) is associated with the worldwide increase of diseases such as cancer, obesity, diabetes, and neurocortical disorders. EDCs are compounds that target the nuclear hormonereceptors (NHR) leading to epigenetic changes. Consequently, the use of biosensing strategies based on epigenetic events have a great potential to provide outstanding information about the exposition of EDCs and their evaluation in human health. This review addresses the novel trends in biosensing EDCs evaluation based on DNA methylation assays associated with different human diseases.