INTRODUCTION: Epilepsy is a common neurological disorder that affects the quality of life globally. Its pathophysiology involves disruptions in ion transport, excitatory-inhibitory imbalances, and regulatory systems. It has been shown that there is a crosstalk between the brain and the gut, where the brain influences the digestive system and the gut can affect brain functions and behavior. This study postulates that probiotic supplementation has both preventive and therapeutic impacts on epilepsy through modulation of inflammatory responses and improvement of brain function. MATERIALS AND METHODS: Male rats were gavaged with three probiotic strains (Lactobacillus reuteri, Bifidobacterium longum, Bifidobacterium lactis) daily for 28 days (10^9 CFU/mL) before inducing epilepsy with pentylenetetrazol (PTZ) injections (37.5 mg/kg every 48 h for 14 injections). Probiotic supplements were continued during disease induction. The effects of probiotics on seizure behavior, histopathology, and pro-inflammatory gene expression were assessed. RESULTS: Probiotic consumption significantly reduced seizure severity, with evident effects from the fourth injection onwards (days 8-28). It delayed the onset of stage 2 and 5 seizures during kindling but had no major effect on stage 5 stability time. Histopathological analysis revealed amelioration of neuronal injury. Besides, there was a significant decrease in the expression of pro-inflammatory genes (Il-1β, Il-6, Ifng) and an increase in the expression of the anti-inflammatory Il-10 in the probiotic-treated model group. CONCLUSION: Probiotics may have both preventive and therapeutic effects on PTZ-induced seizures through reduction of severity of seizures and modulating inflammatory responses. Additional studies are necessary to clarify the mechanisms, as treatment was given before and during kindling.