Treatment of multiple sclerosis is effective when anti-inflammatory, neuroprotective and regenerative strategies are combined. Dendropanax morbiferus (DM) has anti-inflammatory, anti-oxidative properties, which may be beneficial for multiple sclerosis. However, there have been no reports on the effects of DM on myelination, which is critical for regenerative processes. To know whether DM benefits myelination, we checked differentiation and myelination of oligodendrocytes (OLs) in various primary culture systems treated with DM leaf EtOH extracts or control. DM extracts increased the OL membrane size in the mixed glial and pure OL precursor cell (OPC) cultures and changed OL-lineage gene expression patterns in the OPC cultures. Western blot analysis of DM-treated OPC cultures showed upregulation of MBP and phosphorylation of ERK1/2. In myelinating cocultures, DM extracts enhanced OL differentiation, followed by increased axonal contacts and myelin gene upregulations such as Myrf, CNP and PLP. Phytochemical analysis by LC-MS/MS identified multiple components from DM extracts, containing bioactive molecules such as quercetin, cannabidiol, etc. Our results suggest DM extracts enhance OL differentiation, followed by an increase in membrane size and axonal contacts, thereby indicating enhanced myelination. In addition, we found that DM extracts contain multiple bioactive components, warranting further studies in relation to finding effective components for enhancing myelination.