Huntington's disease (HD) is a scarce neurodegenerative disorder defined by chorea (unusual involuntary movements), behavioral presentations, psychiatric features, and cognitive deterioration. Although the precise pathogenic mechanism behind HD has not yet been identified, the most widely acknowledged pathways include excitotoxicity, mitochondrial malfunction, neuroinflammation, neurochemical imbalance, oxidative stress, and apoptosis HD has no efficient therapy. Current medications have drawbacks. Silymarin, a compound made up of standardized extracts obtained from the seeds of the Silybum marianum and polyphenolic flavonolignan, is utilized in therapeutic settings to treat a variety of experimental disorders in animals. Silymarin's key pharmacological activities include anti-cancer, hepatoprotection, antioxidant, cardioprotection, and anti-inflammatory. It also has no adverse side effects on people or animals. The current study aims to provide Silymarin's neuro-pharmacological activities or therapeutic qualities in HD. In this study, Thirty-six male Sprague-Dawley rats (200–220 g, 8 weeks) at the initial of the study were used. Silymarin solution (100 mg/Kg) was administered by oral gavage for 21 days to ameliorate neural damage in rats injected with 3-nitropropionicacid (3-NP) in a preliminary rat model of HD. The results showed that administration of silymarin to HD rats reduced gliosis, improved motor coordination and muscle activity, and increased striatal volume and the number of neurons and glial cells. Our results suggest that silymarin provides a protective environment for nerve cells and can have beneficial effects against the harmful effects of HD.