Valproic acid (VPA) is a drug used for the treatment of epilepsy worldwide. Depending on usage, it can cause complications such as coagulopathies, hepatotoxicity, and encephalopathy. Moringa oleifera has been shown to have antitumor, anti-inflammatory, antiulcer, antispasmodic, diuretic, antihypertensive, antidiabetic, and hepatoprotective activities. The current study investigated the effects of Moringa leaves extract (70% ethanol) on antioxidant systems against valproate-induced oxidative damage in muscle tissues of rats. Female Sprague Dawley rats were randomly divided into four groups. Group I: control group; Group II: animals given only Moringa extract; Group III: animals that received only sodium valproate; Group IV: animals administered with sodium valproate + Moringa extract. Moringa extract and sodium valproate were administered orally. Muscle tissues were collected after sacrificing the animals. Biochemical analysis of muscle tissue homogenates of the valproate group revealed elevated levels/activities of lipid peroxidation, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase, catalase, glutathione reductase, glutathione-S-transferase, reactive oxygen species, total oxidant status, oxidative stress index, glucose-6-phosphate dehydrogenase, sialic acid, protein carbonyl, nitric oxide, and myeloperoxidase. While glutathione, superoxide dismutase, glutathione peroxidase, total antioxidant status, aryl esterase and sodium/potassium ATPase were decreased. The administration of Moringa extract reversed these biochemical changes. These results indicate that Moringa leaves extract had a protective effect on muscle tissues against valproate-induced damage.