Oligodendrocytes (OGDs) are well-established cells in the central nervous system (CNS), primarily recognized for their role in myelination. However, emerging evidence suggests intrinsic differences among OGDs that may lead to diverse functions. OGDs heterogeneity could depend on their origin, location, age, and the presence of pathology. These variations indicate that specific populations of OGDs can modulate local immune responses and interact with other immune cells beyond their role in myelination. OGDs express major histocompatibility complex class I and class II molecules and can thus present endogenous and exogenous antigens to CD8 + and CD4 + T cells, respectively. In physiological conditions, OGDs release factors that maintain microglial quiescence and support homeostatic functions. However, during neuroinflammation, OGDs interact with microglia, astrocytes, and peripheral immune cells infiltrating the CNS, which may change their signaling profiles. In inflammatory conditions, OGDs demonstrate their active role in CNS immunology by producing a range of pro-inflammatory cytokines and chemokines. These factors are critical to the regulation of immune cell migration and activation within the CNS. Conversely, OGDs can also release anti-inflammatory factors, such as brain-derived neurotrophic factors, which help mitigate excessive inflammatory responses. Research into how OGDs affect and are affected by neighboring cells may unveil new therapeutic targets and strategies. The dual roles of OGDs in immunology and CNS function present both opportunities and challenges for advancing our understanding and treatment of CNS disorders.