Oligodendrocytes (OLs) myelinate axons and are essential for fast impulse propagation and the brain’s remarkable processing power. They also carry out important homeostatic support functions that are critical for maintaining long-term neuronal integrity. Mitochondrial reactive oxygen species (ROS) are implicated in various neurodegenerative diseases and influence cell functions in a cell-specific manner, yet the (patho)physiological impact of oligodendroglial ROS on neural functions remains unknown. To study the impact of oligodendroglial ROS in aging and disease, we generated mice (termed OL-mCat mice) in which catalase is specifically overexpressed in OL mitochondria, thereby quenching oligodendroglial ROS levels. We confirmed the expression of HA-tagged catalase in mitochondria of mature OLs in white matter tracts of OL-mCat mice. We could also successfully demonstrate, using flow cytometry employing MitoSox, that mitochondrial ROS levels are specifically reduced in OLs extracted from OL-mCat mice. To assess axonal function, we performed optic nerve electrophysiological recordings of compound action potentials (CAPs). Interestingly, we observed that axonal conduction was better sustained with increasing stimulation frequencies in OL-mCat mice compared to littermate controls in an age-dependent manner. Furthermore, we found that clinical symptoms of EAE were significantly ameliorated in OL-mCAT mice. Hence, our findings imply that suppressing ROS in OLs may protect neural functions in aging and neuroinflammatory disease.