Background: The plant milk thistle and silymarin has been traditionally used as a natural remedy for the treatment of various ailments including neurological disorders such as Alzheimer’s and Parkinson's disease and cerebral ischemia for over 2000 years.Objective: In this article we review the neuroprotective effects of silymarin against various neurological dysfunctions. Results: The neuroprotective effects conferred by silymarin include modulation of various antioxidant mechanisms, and several kinases involved in cell signaling pathways, inhibition of the inflammatory response generated during neurodegeneration, neurotropic effects, regulation of neurotransmitters and inhibition of apoptosis. The ease of availability, comparative low cost and safety profile provide additional advantages for the use of this compound as a potent drug with immense clinical benefit. However, there is a growing need for improvements in the bioavailability of silymarin and related products, and more consistent and reliable human trials are required to accurately validate the neuroprotective efficacy of this natural compound. Conclusion: The promising outcomes of the studies mentioned in this review provide renewed insight into the clinical relevance of silymarin in a variety of neurodegenerative disorders where neuroinflammation and oxidative stress are pathologically relevant to disease progression.