Background: Abnormalities of myelin, which increases the efficiency of action potential conduction, arefound in neurological disorders. Korean Red Ginseng (KRG) demonstrates therapeutic efficacy againstsome of these conditions, however effects on oligodendrocyte (OL)s are not well known. Here, weexamined the effects of KRG-derived components on development and protection of OL-lineage cells. Methods: Primary OL precursor cell (OPC) cultures were prepared from neonatal mouse cortex. Theprotective efficacies of the KRG components were examined against inhibitors of mitochondrial respiratory chain activity. For in vivo function of Rb1 on myelination, after 10 days of oral gavage into adultmale mice, forebrains were collected. OPC proliferation were assessed by BrdU incorporation, and differentiation and myelination were examined by qPCR, western blot and immunocytochemistry. Results: The non-saponin promoted OPC proliferation, while the saponin promoted differentiation. Bothprocesses were mediated by AKT and extracellular regulated kinase (ERK) signaling. KRG extract, thesaponin and non-saponin protected OPCs against oxidative stress, and both KRG extract and the saponinsignificantly increased the expression of the antioxidant enzyme. Among 11 major ginsenosides tested,Rb1 significantly increased OL membrane size in vitro. Moreover, Rb1 significantly increased myelinformation in adult mouse brain. Conclusion: All KRG components prevented OPC deaths under oxidative stress. While non-saponinpromoted proliferation, saponin fraction increased differentiation and OL membrane size. Furthermore, among all the tested ginsenosides, Rb1 showed the biggest increase in the membrane size andsignificantly enhanced myelination in vivo. These results imply therapeutic potentials of KRG and Rb1 formyelin-related disorders.