As more peptide drugs are increasingly entering the market, cell-penetrating peptides (CPPs) have attracted much attention due to their low toxicity, high target specificity and tolerability. CPPs targeting the central nervous system are able to transport therapeutic cargoes across the blood-brain barrier (BBB), offering novel strategies for treating the central nervous system (CNS) disorders, including Alzheimer's disease, Parkinson's disease, brain tumors, and neurotropic viral infections. This review summarizes the structural characteristics of blood-brain barrier-penetrating peptides, elucidates their mechanisms of cellular internalization, and outlines their applications in the treatment of CNS diseases.