Gymnema sylvestre (G. sylvestre), commonly known as gurmar, is famous for the presence of bioactive compounds which make it eligible for use as a medicinal plant. Thus, the purpose of this study is to investigate the potential of G. sylvestre leaf extract in improving the neurotoxic effect of cisplatin (CP). Five groups of rats (6 rats each) were divided into the control group, the gurmar group (administrated orally 100 mg/kg bw), the CP group receiving a single intraperitoneal injection of 5 mg/kg bw), the CP + gurmar group, and the gurmar + CP group. After 12 days (the experiment period), the brains of rats were removed and stored to evaluate biochemical parameters. CP injection led to elevated levels of malondialdehyde (MDA), nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), and apoptosis (caspases 8, 9, and 12) and to the decrease in the activities of antioxidant enzymes (catalase and superoxide dismutase) and neurotrophin (nerve growth factor and brain-derived neurotrophic factor) levels in brains of rats. On the other hand, administration of G. sylvestre leaf extract decreased MDA, NF-κB, TNF-α, and apoptosis levels and increased antioxidant enzymes activities and neurotrophin levels in the brains of rats injected with CP. This study demonstrated the ability of G. sylvestre leaf extract to counteract the neurotoxicity induced by CP through its antioxidant, anti-inflammatory, and anti-apoptotic activities.