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Parkinson’s disease stands as the second most common neurodegenerative disorder worldwide. This study aimed to assess the impact of DMSO in a rotenone-induced rat model of Parkinson’s disease. DMSO has become a popular agent in preclinical and clinical studies due to its ability to facilitate the transport of poorly soluble drugs across the blood-brain barrier. In this investigation, we explored how a three-week treatment with rotenone, combined with DMSO, influenced hippocampal neuronal activity and the properties of neuronal responses in rats. We specifically compared the toxic effects of rotenone on hippocampal CA1 and CA3 neurons in the presence of DMSO. Our results showed that rotenone induced substantial morphological changes in hippocampal cells. Following DMSO treatment, however, there was a significant restoration of pyramidal cells and Nissl bodies within the CA1 and CA3 regions. DMSO also effectively suppressed both outward and inward currents. Additionally, we recorded spontaneous and evoked spike activity in the hippocampus of rats treated with DMSO (1 ml/kg, administered intraperitoneally for 3 weeks). While rotenone elevated TP and produced a moderate TD effect, DMSO also increased TP but produced a more pronounced TD effect. The analysis indicated inhibitory responses in the hippocampus following high-frequency stimulation (100 Hz for 1 second) of the ipsilateral entorhinal cortex.