Central nervous system demyelinating diseases, represent a group of chronic autoimmune conditions requiring long-term intervention. Traditional systemic administration methods face limitations due to the blood-brain barrier, resulting in issues such as low central nervous system delivery efficiency, high systemic exposure, and significant interindividual pharmacokinetic variability. These factors compromise treatment precision and patient compliance. The Nose-to-Brain (N2B) route bypasses the blood-brain barrier via the olfactory and trigeminal pathways, enabling direct central drug delivery with advantages including non-invasiveness, high targeting specificity, and minimal systemic side effects. This study systematically reviews the dual-pathway delivery mechanism of this route, along with recent advances in reducing neuroinflammation, promoting myelin regeneration, and neuroprotective delivery strategies. It also analyzes current challenges in clinical translation.