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.