Epilepsy is one of the most common neurological disorders that severely affect the life quality of many people worldwide. Excitatory-inhibitory mechanisms, oxidative stress, and also inflammation systems have been implicated in the pathogenesis of epilepsy. Recent studies have shown that salmon calcitonin (sCT) has positive effects on the nervous system. However, its relation with epilepsy is still unclear. This study aimed to investigate the effect of sCT on epileptic seizures, epileptogenesis, and postseizure hippocampal neuronal damage in pentylenetetrazole (PTZ)-induced epilepsy model in rats. The study was performed in two steps. In the first step, the effect of sCT on epileptic seizures was evaluated by using electroencephalography (EEG) in fully kindled rats. In the second step, the effect of sCT on epileptogenesis was evaluated by using the kindling process. Glutamate and gamma-aminobutyric acid (GABA), thiobarbituric acid reactive substance (TBARS), superoxide dismutase (SOD), catalase (CAT), tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) were measured in the second group in the brain and serum. Hippocampal regions were stained with hematoxylin-eosin and toluidine blue to evaluate hippocampal neuronal damage histopathologically. Salmon calcitonin showed an antiepileptic effect in fully kindled rats and also prevented the development of epileptogenesis in the kindling process. Besides, sCT decreased glutamate and increased GABA levels. Furthermore, it reduced TBARS levels and increased SOD and CAT levels. On the other hand, it decreased TNF-alpha levels, IL-1 beta levels, and IL-6 levels. Histopathologically, sCT decreased neuronal damage in all hippocampal regions. Our findings are the first preclinical report to show the positive effect of sCT on epileptic seizures and epileptogenesis. Further investigation is required to answer the questions raised about the probable mechanisms involved. (C) 2020 Elsevier Inc. All rights reserved.