In recent years, nanotechnology-based approaches have emerged as promising strategies for improving drug delivery to the brain. Specifically, nanoparticles (NPs) decorated with cell-penetrating peptides (CPPs) have attracted considerable attention for their potential to overcome the blood-brain barrier (BBB) and facilitate efficient nose-to-brain delivery. This chapter highlights studies described in the literature involving the development of CPP-decorated nanoparticles for nose-to-brain delivery that focus on the treatment of CNS diseases. Furthermore, the strategies/methods for developing and testing these nanoparticles will be reviewed, and the challenges associated with brain drug delivery and the potential of CPP-based strategies to overcome the obstacles will be discussed.