Current　therapeutic　strategies　for　autoimmune　diseases　such　as　multiple　sclerosis　(MS)　are　directed　towards　nonspecific　immunosuppression,　which　has　severe　side　effects.　The　induction　of　antigen-specific　tolerance　has　become　an　ideal　therapy　for　autoimmune　diseases.　In　this　study,　we　have　constructed　a　dual　peptide　nanoparticle　platform,　including　the　antigen　peptide　of　the　primary　signal　and　inhibitory　peptide　of　the　co-stimulatory　signal,　for　T-cell　activation　and　to　trigger　antigen-specific　immune　tolerance　to　treat　experimental　autoimmune　encephalomyelitis　(EAE),　a　murine　model　for　MS.　The　peptide　LABL　binding　with　ICAM-1　was　encapsulated　in　PLGA　nanoparticles　and　the　antigenic　peptide　MOG(35-55)-KKK　was　then　covalently　bonded　to　the　surface　of　the　PLGA　nanoparticles.　In　this　way,　peptide-loaded　PLGA　nanoparticles　(NPs(LABL+MOG))　were　developed.　When　the　dual　peptide　nanoparticles　were　administered　intravenously　either　prophylactically　or　therapeutically　to　MOG(35-55)-immunized　mice,　it　completely　prevented　the　occurrence　of　EAE　in　the　prophylactic　therapy　trial　and　decreased　inflammatory　cell　infiltration　and　the　demyelination　of　the　nerve　myelin　in　the　spinal　cord　in　both　prophylactic　and　therapeutic　trials.　In　therapeutic　experiments　especially,　the　dual　peptide　nanoparticles　a　showed　stronger　inhibitory　effect　on　EAE　than　the　MOG　peptide　nanoparticles　alone.　Mechanistically,　the　dual　peptide　nanoparticles　reduced　MHC　II　and　the　co-stimulatory　molecule　CD86　expression　of　dendritic　cells　(DCs)　on　the　surface　and　induced　abortive　T-cell　activation,　which　eventually　led　to　a　decreased　infiltration　of　Th1　and　Th17　cells　in　the　central　nervous　system　and　showed　antigen-specific　immune　tolerance.　The　dual　peptide　nanoparticles　have　great　potential　for　the　treatment　of　autoimmune　diseases　by　inducing　immune　tolerance.