Arsenic is one of the toxic metalloid that is ubiquitously distributed in environment that exerts toxic effects by contaminating air, water, soil, and other resources. Groundwater is thought to be the major source of arsenic-induced mammalian toxicity. The current work sheds light on the antioxidant and anti-inflammatory properties of silymarin against arsenic-induced neurotoxicity in rats. Male albino wistar rats were categorized into 4 groups i.e., control, silymarin-treated (50 mg/kg), arsenic-treated (25ppm), and arsenic + silymarin-treated. Arsenic and silymarin were given intragastrically for 28 days. The study found that as compared to the control rats, animals that received arsenic treatment had lower levels of total antioxidants inside their brain tissues. Additionally, a notable rise in malondialdehyde level, protein oxidation, and inflammation was observed in the group of arsenic treatment suggesting oxidative stress generation inside brain tissue of rats leading to neuronal damage. However, silymarin reversed the damage caused by arsenic in rats, demonstrating its anti-inflammatory and antioxidant potential. The electron microscopic and histological results also showed that silymarin reversed the neuronal damage induced by arsenic exposure providing additional evidence of its antioxidative nature. The present study highlights the therapeutic efficacy of silymarin as an antioxidant against arsenic-induced toxicity in rats' brain.