It is clear that a wide spectrum of human diseases is a function of epigenome modulation. Environmental factors and lifestyle particularly nutrition can modify the regulation of the epigenome. Bioactive peptides (BAPs) driving from different sources such as food sources, animal sources, vegetal sources, and exogenous sources. They affect epigenome regulation through undergoing changes of DNA methylation, histone acetylation, non-coding RNAs, and miRNAs. Bioactive derived food peptides with epigenetic effects can be a contributing factor in different medical conditions such as cancer, cardiovascular diseases (CVDs), neurological and neurodegenerative disorders, chronic obstructive pulmonary disease (COPD), and type 2 diabetes (T2DM).