Display omitted Since the application of chitosan magnetic cationic microspheres in brain drug delivery by Gallo in 1993, chitosan has been extensively studied in brain drug delivery. As the only natural alkaline polysaccharide with good biocompatibility and biodegradability, chitosan prepared nanoparticles which use chitosan as carrier material to encapsulate drug have been proved with advantages of protecting from enzyme degradation, control release and improved bioavailability. Besides, chitosan can enhance drug permeability across the blood-brain barrier by affecting the tight junction. And with positive charge on the surface, chitosan nanoparticles can absorb on the negatively charged cell membrane, thus increase its residence time on the nasal mucosa and benefit of the delivery of drugs from the nasal cavity to the brain. All these properties made chitosan nanoparticles especially suitable for brain delivery. What’s more, the free amino groups on the surface of chitosan nanoparticles allow specific chemical modification to form a wide range of chitosan derivatives. Surface modification of the nanoparticles with tumor targeting peptides like chlorotoxin and transferrin, can further improve the targeting property to brain tumor. This article gives a comprehensive review on the advantages and recent progresses in the treatment of brain disease by chitosan nanoparticles.