Glioma is the most common malignant tumor in the central nervous system. The clinical treatment strategy is mainly surgery combined with concurrent temozolomide chemotherapy, but patients can develop drug resistance during treatment, which severely limits its therapeutic efficacy. Epigenetic regulation at the RNA level is plastic and adaptable, and it can induce a variety of tumor responses to drugs. The regulators of RNA modification include methyltransferases, demethylases, and methylation binding proteins; these are also considered to play an important role in the development, prognosis, and therapeutic response of gliomas, which provides a basis for finding new targets of epigenetic drugs and resetting the sensitivity of tumor cells to temozolomide. This review discusses the relationship between the development of adaptive drug resistance and RNA modification in glioma and summarizes the progress of several major RNA modification strategies in this field, especially RNA m6A modification, m5C modification, and adenosine-to-inosine editing.