Background: Vitiligo is a depigmenting skin condition characterized by specific melanocyte depletion, resulting in the attenuation of melanin within the affected skin regions. Mitochondrial dysfunction and oxidative stress have been implicated in the pathogenesis of vitiligo. This study aimed to investigate the gene expression levels of Uncoupling Protein 2 (UCP2) and Dynamin-related Protein 1 (Drp1) in vitiligo patients and their potential association with disease severity and activity. Methods: This case- control study was conducted, including 40 vitiligo patients and 40 age and sex-matched healthy controls. Gene expression levels of UCP2 and Drp1 were measured in plasma samples using an enzyme-linked immunosorbent assay (ELISA). Results: The study included 40 patients with vitiligo. Their mean age was 28.9 years. They were 77.5% males and 22.5% females. In addition to 40 healthy control subjects od matched age and gender (p≥ 0.05). The study revealed significant downregulation of UCP2 gene expression and upregulation of Drp1 gene expression in vitiligo patients compared to healthy controls. Conclusions: The findings suggest that dysregulation of UCP2 and Drp1 gene expression may play a role in the pathogenesis of vitiligo.