It is unclear whether left and/or right side lesions of mesial temporal lobe epilepsy (MTLE) exhibit different degrees of brain aging. Therefore, we developed machine-learning-based brain age models to quantify the brain aging of patients with unilateral MTLE and of healthy controls. The significantly overestimated brain age was found in the right but not left MTLE patients. Also, the degree of overestimated brain age was correlated with the clinical factors. Moreover, the right uncinate fasciculus was the most contributing feature to the overestimated brain age. This study uncovered the underpinning of advanced brain aging in right MTLE patients.