Peroxisomes generate reactive oxygen species (ROS) and also play a role in protecting cells from the damaging effects of such radicals. Dysfunctional peroxisomes are recognized by receptors and degraded by a selective type of macroautophagy called pexophagy. Oxidative stress is one of the signals that activates pexophagy through multiple signaling pathways. Conversely, impaired pexophagy results in the accumulation of damaged peroxisomes, which in turn leads to elevated ROS levels and oxidative stress, resulting as cellular dysfunction and the progression of diseases such as neurodegeneration, cancer, and metabolic disorders. This review explores the molecular mechanisms driving pexophagy and its regulation by oxidative stress with a particular focus on ROS. This highlights the role of peroxisomal proteins and ROS-mediated signaling pathways in regulating pexophagy. In addition, emerging evidence suggests that the dysregulation of pexophagy is closely linked to neurological disorders, underscoring its potential as a therapeutic target. Understanding the intricate crosstalk between pexophagy and oxidative stress provides new insights into the maintenance of cellular homeostasis and offers promising directions for addressing neurological disorders that are tightly associated with pexophagy and oxidative stress.