Multiple　sclerosis　(MS)　is　caused　by　an　aberrant　autoimmune　response　in　the　central　nervous　system　(CNS),　which　results　in　progressive　demyelination.　Current　therapies,　mostly　disease　-modifying　therapies,　have　limited　wide　use　due　to　their　higher　costs,　low　patient＇s　compliance,　and　serious　side　effects.　Here,　we　firstly　show　that　nano　-sized　gold　clusters　(GA,　molecular　formula　Au29SG27)　can　significantly　attenuate　or　reverse　clinical　symptoms　and　prevent　neuronal　demyelination　in　an　experimental　autoimmune　encephalomyelitis　(EAE)　mouse　model　of　MS　when　administered　prophylactically　or　therapeutically.　GA　reduces　the　infiltration　of　Th1　and　Th17　cells,　and　the　secretion　of　associated　pro　-inflammatory　cytokines　in　the　CNS.　Notably,　GA　shows　potent　direct　inhibitory　activity　on　the　differentiation　of　CD4+　T　cells　into　Th1　and　Th　17　in　vitro　with　no　effect　on　apoptosis　and　activation　of　T　cells.　Mechanistic　studies　show　that　GA　inhibit　JAK/STAT　signaling,　which　is　critical　for　Thcell　differentiation,　through　specific　Au　-binding　with　JAK　protein　in　cells.　Collectively,　our　results　sheds　light　on　GA　as　a　novel　nano　-drug　for　MS　treatment　with　low　toxicity　and　high　efficiency.