Human MutT homolog 1 (MTH1) plays a crucial role in sanitizing oxidized DNA precursors by enzymatically hydrolyzing oxidized nucleotides. The absence of MTH1 activity in the cells results in the accumulation of oxidized nucleotides within the nucleus and mitochondria, leading to mutations, abnormal proteins, and neurodegeneration (in the central nervous system). It has garnered interest as a potential target for anticancer treatment through targeted inhibitor molecules but remains largely understudied in other neurological disorders. This review explores the understanding of MTH1 expression in glioma and its potential role in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease concerning disease mechanism and prognosis. Neurodegeneration, activation of glial cells, and mitochondrial dysfunction are common mechanisms involved in the progression of these diseases. This review also tries to identify the unexplored associations and research gaps that can reveal novel applications of the enzyme in epilepsy, in which MTH1 is studied less. The influence of the ROS environment and cell type on MTH1 expression and function is crucial to be studied for elucidating its role in a multitude of CNS pathologies. The involvement of microglial cell-mediated inflammatory responses through ROS production in epileptogenesis in mouse models highlights the interplay between oxidative stress and neuroinflammation in epilepsy. The possible existence of a similar association between MTH1 expression and pathogenesis of the discussed neurological disorders in vivo demands further exploration preclinically and in patient samples.