Background: Monosodium glutamate (MSG) is one of the most used food additives that disrupt the metabolism and the functions of many organs, including the heart, liver, brain, and others.Jojoba is a plant with high oil content in its seeds and special antioxidant and anti-inflammatory characters that make it convenient for medical uses as a natural plant. GLUT 4 is useful for "deep" glucose transport during raised energy demand. Aim: To evaluate the antioxidant activity of jojoba oil and its role against MSG-induced toxicity in rats by improving metabolic dysfunction in the brain and heart and minimizing pathological changes. Materials and Methods: Thirty-two male albino adult rats were assigned randomly to four equal groups. Group I was given distilled water (control group). Group II  was given a standard diet with 2.5 percent jojoba oil added. MSG (4 g/kg) dissolved in distilled water was given orally to group III. Group IV received MSG (4g/kg) diluted in distilled water and was also fed a basic diet with 2.5 percent jojoba oil. After two months, blood samples were taken to measure the expression of NFκB and GLUT4 genes, free fatty acids (FFA), troponin I, CK-MB, cytokines, oxidative stress markers, and GABA neurotransmitters. Histopathological study of the heart and brain tissues was also done. Results: MSG increases NF κB expression, Troponin I, CK-MB, FFA, TNFα, IL6, Caspase3, and MDA compared to normal control rats. Significant depletion of Catalase, GABA neurotransmitter with downregulation of GLUT4 gene expression was noted. Histopathological alterations in the brain and cardiac tissues of MSG-treated rats were also noted. In contrast, treatment with jojoba oil greatly attenuated these toxic effects. Conclusion: Because of its antioxidant properties and ameliorating metabolic properties, jojoba oil showed significant protection against MSG-induced cardiac and neurotoxicity.