This study systematically reviewed the significance of GABAergic MG, glyoxalase I (GLO1), which is responsible for the enzymatic catalysis of MG cleavage, and downstream RAGE signaling in epilepsy and discussed the potential of miRNAs with the goal of establishing groundwork for future research aiming to reconcile the conflicting effects of MG on epileptic seizures. This evidence concerns the gene GLO1 and epilepsy.