There is growing evidence linking epigenetic mutations to neurologic disorders such as epilepsy. The effect of the medications primarily used to treat neurologic disorders has recently been studied, including research on epilepsy and the epigenetic process. The impact of the widely used medication diazepam on epigenomics, microRNA levels, the ensuing genetic exposure and potential clinical effects was reviewed. The action of diazepam, particularly in altering the synthesis of enzyme 5'adenosine monophosphate activated protein kinase (AMPK) was found to affect many enzymes, which changes or modifies the epigenetics. Epigenetic enzymes such as histone acetyltransferases (HATs), class II histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) are mainly activated by AMPKs, including the phosphorylate substrates, which often lead to their inhibition, although HAT1 activity may be improved. It has been reported that diazepam can reduce histone methyltransferase expression exposure, may increase class III histone deacetylases activity and may decrease the effect of DNA methyltransferases inhibitors. Diazepam has been found to contribute to mutations of the epigenome and genetic expression, and may protect against neurologic disorders, aging, dementia and several brain diseases. It has also been found that microRNA expression can be influenced by diazepam treatment and may have neurologic effects. Although the reported effects of diazepam on epigenetic enzymes of are equally effective in both amplifying and reducing acetylation of histone, histone and DNA methylation and gene expression, the effect of diazepam on the epigenome, genetic expression, and subsequent effects in all healthy diazepam users is unclear.