Our results demonstrate the potential of COXP micelles for delivering therapeutic, preventative, or diagnostic agents to the brain. Display omitted •Blood brain barrier (BBB) is the major cause of treatment failure for most brain diseases.•The BBB is enriched with glutathione (GSH) transporters.•COXP was designed by connecting a GSH to a cholesterol through a short chain.•COXP is a GSH transporter-based brain targeting agent.•COXP self-assembles to form brain targeting micelles (COXP micelles).•COXP micelles delivered DiR to a mouse brain 20 folds higher than DiR alone.•GSH further increased COXP micelles’ brain-targeting in mice by more than one-fold. The blood–brain barrier (BBB) is a barrier that prevents almost all large and most small exogenous molecules from reaching the brain. The barrier is the major cause of treatment failure for most brain diseases. Extensive efforts have been made to facilitate drug molecules to cross the BBB. One of the approaches is to employ an endogenous ligand or ligand analogue that can enter the brain through its transporter or receptor at the BBB as a brain-targeting agent. Glutathione (GSH) transporters are richly expressed at the BBB with limited presence in other tissues except kidneys. 2-(2-Cholesteroxyethoxyl)ethyl 3′-S-glutathionylpropionate (COXP), formed by connecting GSH with cholesterol through a linker, was designed as a GSH transporter-mediated brain targeting molecule. The amphiphilic nature of COXP enables the molecule to self-assemble to form micelles with a CMC value of 3.9 μM. By using DiR as a fluorescence tracking agent and the whole-body fluorescence imaging technique, the brain distribution of DiR delivered by COXP micelles in mice was 20 folds higher when compared with free DiR. Interestingly, the brain targeting effect was further enhanced by co-administration of GSH. The low CMC value and effective brain targeting make COXP micelles a promising drug delivery system to the brain.