Oligodendrocyte precursor cells (OPCs) are one of the major cell types in cerebral white matter, which are generated from neural progenitor cells (NPCs) and give rise to mature oligodendrocytes. Although past studies have extensively examined how OPCs are generated from NPCs and how OPCs differentiate into mature oligodendrocytes, the underlying mechanisms remain unelucidated. In particular, the roles of DNA methylation and the related enzymes DNA methyltransferases (DNMTs) in oligodendrocyte lineage cells are still mostly unknown, although DNA methylation plays a critical role in cell fate decision in multiple cell types. Recently, OPCs were proposed as a promising source of cell-based therapy for patients with oligodendrocyte/myelin damage. Therefore, understanding the mechanisms underlying the involvement of DNMTs in OPCs would help to develop an approach for the efficient preparation of OPCs for cell-based therapy. As a part of the special issue for "Stem Cell Therapy" in Brain Research, this mini-review article first overviews the potential for clinical application of OPCs for cell-based therapy, and then summarizes the key findings of DNMT roles in OPCs, focusing on OPC generation and differentiation.