<p>The effective delivery of neuroprotective therapeutics to the brain remains a major challenge in the treatment of neurological disorders because the blood–brain barrier (BBB) restricts the entry of most small molecules, biologics, and nucleic acid-based agents into the central nervous system. This mini-review critically evaluates ligand-directed nanocarriers as mechanistically informed platforms for brain-selective neuroprotection, with particular emphasis on the conditions under which receptor engagement yields productive transcytosis rather than simple endothelial association. Rather than providing a descriptive catalogue of ligands and carriers, the review examines how receptor accessibility, affinity/avidity balance, ligand density, PEG shielding, cargo properties, and disease-dependent BBB heterogeneity jointly determine brain exposure and therapeutic performance. Representative preclinical studies are interpreted using quantitative endpoints that link delivery to pharmacological effect, including regional brain AUC, infarct limitation, suppression of neuroinflammatory cytokines, reduction of amyloid burden, preservation of dopaminergic neurons, and functional recovery. The analysis indicates that apparent delivery gains are strongly study-dependent and should not be generalized as intrinsic advantages of any single ligand or carrier class. On this basis, the review proposes a translational framework centered on mechanistic assay rigor, scalable manufacturing, repeat-dose safety, and validation in human-relevant BBB models as the key determinants of clinically credible brain-selective neuroprotection.</p>