As current treatments for multiple sclerosis (MS) remain chemotherapeutic ones directed toward symptoms, the development of a curative treatment is urgently required. Herein, we show an autoreactive immune cell-targetable approach using autoantigen-modified liposomes for the curative treatment of MS. In these experiments, experimental autoimmune encephalomyelitis (EAE) induced by autoantigenic myelin oligodendrocyte glycoprotein (MOG) peptide was used as a model of primary progressive MS, and MOG-modified liposomes encapsulating doxorubicin (MOG-LipDOX) were used as a therapeutic drug. The results showed that the progression of encephalomyelitis symptoms was significantly suppressed by MOG-LipDOX injection, whereas the other samples failed to show any effect. Additionally, invasion of inflammatory immune cells into the spinal cord and demyelination of neurons were clearly suppressed in the MOG-LipDOX-treated mice. FACS analysis revealed that the number of both MOG-recognizable CD4 T cells in the spleen was obviously decreased after MOG-LipDOX treatment. Furthermore, the number of effector Th17 cells in the spleen was significantly decreased and that of regulatory Treg cells was concomitantly increased. Finally, we demonstrated that myelin proteolipid protein (PLP)-modified liposomes encapsulating DOX (PLP-LipDOX) also showed the therapeutic effect on relapsing-remitting EAE. These findings indicate that autoantigen-modified liposomal drug produced a highly therapeutic effect on EAE by delivering the encapsulated drug to autoantigen-recognizable CD4 T cells and thus suppressing autoreactive immune responses. The present study suggests that the use of these autoantigen-modified liposomes promises to be a suitable therapeutic approach for the cure of MS.