Aim:To assess the therapeutic effects of methylprednisolone, nimodipine, and amantadine on peripheral nerve injury using a rat sciatic nerve compression model, simulating potential treatments for humansMaterial and Methods:A total of 36 adult male Wistar albino rats were divided into five groups. In Group 1, right sciatic nerve compression was performed, while the left side was used as a sham group (Group 2). Groups 3, 4 and 5 received methylprednisolone, nimodipine or amantadine for one week following injury. In histopathologic analysis, nerve diameter, myelin diameter, axon diameter, G ratio, fibroblast count, mast cell count and nerve number were measuredResults:Significant differences were observed across the groups. Amantadine showed the most positive effects on nerve regeneration, improving nerve diameter, myelin diameter, G ratio, fibroblast number, and nerve number compared to controls. Nimodipine was effective in improving nerve diameter and G ratio but had no effect on other parameters. Methylprednisolone showed significance only in the G ratio. No drug was found superior to the others when compared in combination. Overall, amantadine had the most positive cellular effects after sciatic nerve injury, though further research is required to explore optimal dosage, frequency, administration route, and additional clinical parametersConclusion:In this study, amantadine was found to have the most favorable effects on nerve regeneration, but other drugs showed limited effects on some parameters. However, the lack of superiority in combined applications and the lack of clarification of ideal treatment conditions suggest the need for more comprehensive research in the future.