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Silymarin is polyphenolic flavonoid obtained from the seeds of silybum marianum plant. It has various pharmacological properties such as hepatoprotective, anti-inflammatory, antioxidant, anti-carcinogenic, hypolipidemic properties. Silymarin has recently reported to be neuroprotective agent against neurodegenerative disease such as Alzheimer, Parkinson’s and cerebral ischemia. It contains eight active components, among which silibinin is the most active component. However, silymarin is BCS class II drug which having poor bioavailability due to extensive phase II metabolism, poor aqueous solubility, low permeability across intestinal epithelial cells and rapid excretion in bile and urine. Therefore, it is necessary to understand all formulations and analytical aspects including all possible future prospects. In this review a potential approach to enhance solubility, bioavailability and to develop a robust formulation is studied. The number of studies describes novel drug delivery system (NDDS) based formulations have been significantly increased. The raise in novel drug delivery exploitation is essentially due to defeated barriers within technological process of lipid based nanoparticles formulations and increased knowledge of underlying mechanisms of transport of NDDS via different route of administration. This review focuses on pharmacological properties of silymarin, challenges, benefits and application of novel drug delivery system. To reduce the adverse effects and toxicities novel drug delivery will be an attractive approach of current therapies. Keywords: Silymarin, route of administration, novel drug delivery, bioavailability, solubility