ABSTRACT Aims Although the genetic locus of X‐linked dystonia parkinsonism (XDP), a neurodegenerative disease endemic in the Philippines, is well‐characterized, the exact mechanisms leading to neuronal loss are not yet fully understood. Recently, we demonstrated an increase in myeloperoxidase (MPO) levels in XDP postmortem prefrontal cortex (PFC), suggesting a role for inflammation in XDP pathogenesis. Therefore, we hypothesized that inhibiting MPO could provide a therapeutic strategy for XDP. Methods MPO activity was measured by using an MPO‐activatable fluorescent agent (MAFA) in human postmortem PFC. Reactive oxygen species (ROS) and MPO activity were measured in XDP‐derived fibroblasts and SH‐SY5Y cells following MPO inhibition. Results MPO activity was significantly increased in XDP PFC. Additionally, treatment of cell lines with postmortem XDP PFC resulted in a significant increase in ROS levels. To determine whether increases in MPO activity caused increases in ROS, MPO content was immunodepleted from XDP PFC, which resulted in a significant decrease in ROS in SH‐SY5Y cells. Consistently, the treatment with verdiperstat, a potent and selective MPO inhibitor, significantly decreased ROS in both XDP‐derived fibroblasts and XDP PFC‐treated SH‐SY5Y cells. Conclusions Collectively, our results suggest that MPO inhibition mitigates oxidative stress and may provide a novel therapeutic strategy for XDP treatment.