Multiple sclerosis (MS) is a neurodegenerative disease characterized by immune-mediated damage to the myelin sheath resulting in physical and cognitive disability. While current treatments are effective at reducing disease relapse, there are no treatments available that prevent disease progression. Recent studies have reported that activating the kappa opioid receptors (KOR) with the KOR agonist, U50,488, is beneficial in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Unfortunately, U50,488 is not suitable for clinical use due to its poor side-effect profile. However, we have found that nalfurafine, a potent and well-tolerated KOR agonist, which is in clinical use, enabled full recovery, enhanced remyelination, and reduced neuroinflammation in EAE when administered therapeutically (i.e. after disease onset). Additionally, nalfurafine was more effective than U50,488 and mediated full recovery from EAE in a KOR-dependent fashion. Finally, nalfurafine promoted remyelination in the cuprizone model of non-immune demyelination, supporting the direct effect on remyelination in the absence of peripheral immune cell invasion. Overall, our findings support the potential of nalfurafine to promote recovery and remyelination and highlight its promise for clinical use in MS.