Epilepsy is a disorder characterized by an imbalance between excitability and inhibition, leading to uncontrolled hyperexcitability of neurons in the central nervous system. Despite the prevalence of epileptic seizures, the underlying mechanisms driving this hyperexcitability remain poorly understood. This review article aims to enhance our understanding of the mechanisms of epilepsy, with a specific focus on the role of cholecystokinin (CCK) in this debilitating disease. We will begin with an introduction to the topic, followed by an examination of the role of GABAergic neurons and the synaptic plasticity mechanisms associated with seizures. As we delve deeper, we will elucidate how CCK and its receptors contribute to seizure behavior. Finally, we will discuss the CCK-dependent synaptic plasticity mechanisms and highlight their potential implications in seizure activity. Through a comprehensive examination of these aspects, this review provides valuable insights into the involvement of CCK and its receptors in epilepsy. By improving our understanding of the mechanisms underlying this condition, particularly the role of CCK, we aim to contribute to the development of more effective treatment strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)