Methylmercury (MeHg), an organometallic contaminant is a well spotted cause for a series of disorders, especially in the central nervous system. As there is no proper treatment, Selinum vaginatum (Edgew) C. B. Clarke, a traditional medicinal plant, is taken in the present study for assessing its neuroprotective effect against MeHg induced toxicity using rat brain mitochondrial fractions. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide dye (MTT) assay indicated that there was a reduction in the mitochondrial viability in MeHg treated sample and IC50 value recorded was 2.5μg/ml. Biochemical analysis showed that there was a significant inhibition of glutathione levels (GSH) and catalase activity and an elevation of thiobarbituric acid reactive substances (TBARS) levels in MeHg treated sample. These changes were prevented by co-incubation with essential oil extracted from Selinum vaginatum. The GSH reduction caused by MeHg is restored by essential oil, endorsing its chelating effect, an important molecular mechanism of defense against oxidative injury. Some of the major compounds are detected in Gas chromatography-mass spectrometry (GC-MS) analysis of essential oil, which could be accountable for its neuroprotection against MeHg. © Pakistan Journal of Pharmaceutical Sciences. All rights reserved.