The blood–brain barrier (BBB) keeps the central nervous system (CNS) safe from various brain diseases, while the BBB makes it difficult for effective drugs to enter the CNS. Mfsd2a is specifically expressed on the cell membrane of brain-microvascular endothelial cell (BMEC) and is implicated in the delivery of some substances across the BBB. Mfsd2a is the first inhibitor of the transcytosis and the first transporter for lysophosphatidylcholine-docosahexaenoic acid (LPC-DHA) in BMECs. The crucial dual function of Mfsd2a puts forward two kinds of Mfsd2a-based strategies for carrying drugs from blood to the CNS. First, the reversible inhibition of Mfsd2a may temporarily induce a general disinhibition of the transcytosis in BMECs to transport macromolecular drugs across the BBB (Strategy One). Second, Mfsd2a could be used for the transport of some small-molecule drugs chemically coupled to LPC across the BBB (Strategy Two), which is quite similar to the carrier-mediated transport (CMT) via the glucose transporter (GluT1) and the L-type amino acid transporter 1 (LAT1). We here analyze and discuss the clinical significance of the two Mfsd2a-based strategies, including therapeutic potential, available pharmaceuticals, side effects, administration procedures, and disease types. In summary, the regulatory role of Mfsd2a deepens our knowledge of the function of the BBB, potentially contributing to the effective drug delivery in the treatments for neurodegenerative diseases, brain tumors, and life-threatening infections in the CNS.