The blood-brain barrier (BBB) plays an irreplaceable role in protecting the central nervous system (CNS) from bloodborne pathogens. However, the BBB complicates the treatment of CNS diseases because it prevents almost all therapeutic drugs from getting into the CNS. With the growing understanding of the physiological characteristics of the BBB and the development of nanotechnology, nanomaterial-based drug delivery systems have become promising tools for delivering drugs across the BBB to the CNS. Herein, we systematically summarize the recent progress in organic-nanoparticle delivery systems for treating CNS diseases and evaluate their mechanisms in overcoming the BBB with the aim to provide a comprehensive understanding of the advantages, disadvantages, and challenges of organic nanoparticles in delivering drugs across the BBB. This review may inspire new research ideas and directions for applying nanotechnology to treat CNS diseases.