<p>The human brain acts as a crucial organ that requires a high glucose metabolic content. However, abnormal glucose levels act as a major factor for frequent epileptic foci. Thus, it has come to attention in the recent past that epilepsy is a metabolic problem in addition to a neurological condition. However, several studies have postulated a link between epilepsy and diabetes mellitus, but very few have emphasized the exact molecular mechanism behind it and its related specific targets. Hence, this article mainly outlines in-depth knowledge about the molecular mechanisms involved and its associated target approaches. Data from several publications, such as meta-analysis, systematic and narrative reviews, and research papers obtained from electronic databases, have been used for postulating a strong evidence in order to establish a comprehensive article addressing this problem in depth. The data discussed here have revealed how adiponectin levels and mitochondrial activity impact obesity, type 2 diabetes mellitus (T2DM), and epilepsy. We have also tried to give a brief idea about the possible theories that would also impact the severity of these two conditions, including adequate exercise and the impact of commonly used AEDs. Furthermore, one of the factors causing genetic predisposition to seizures due to glucose metabolism, such as GLUT-1 deficiency, has also been described briefly. It has to be mentioned that researchers and clinical practitioners might need to take these factors into account while discovering and evaluating a suitable novel therapeutic in the future.</p> Graphical Abstract <p></p>