Brain tumors are one of the most severe types of malignant tumors and glioma accounts for ~80% of malignant brain tumors. The current treatment methods for glioma are limited and patients with glioma often experience relapse following treatment, which leads to a poor prognosis for these patients. Therefore, novel therapeutic targets and methods urgently need to be explored. The present review screened studies that mainly focused on the epigenetic regulation of small guanosine triphosphate (GTP)ase in glioma. These small GTPases participate in most cellular biological processes, including differentiation, proliferation, cell migration, apoptosis, vesicle and organelle dynamics and transport, nuclear dynamics and cytoskeleton regulation. Due to the diversity and importance of the biological functions of small GTPases, an increasing number of studies have focused on them; however, the incidence of changes in the gene structure of small GTPases is considered to be low in glioma. Several studies have shown that the abnormal expression of genes encoding small GTPases is often influenced by epigenetic regulation in glioma. Epigenetic regulation is a dynamic and reversible process, which implies that the reversal of abnormal epigenetic modifications is a potential treatment strategy for glioma. These previous studies, which are summarized in the present review, not only provide new therapeutic targets and prognostic markers, but also provide information regarding the treatment of glioma. The current review may provide valuable insights for future research and promote the clinical translation of relevant research results.