Malignant gliomas are the most lethal form of brain cancer, characterized by rapid cell growth, substantial molecular heterogeneity, and a propensity for invasion into critical brain regions. Phosducin (PDC) is recognized for its involvement in sensory signal transmission, blood pressure regulation, and thyroid gland endocrine functions. However, the role of PDC in cell proliferation, drug sensitization, and its connection to RNA m6A modification in gliomas remains unclear. In this study, RNA sequencing analysis was performed on U251 glioma cells with knockdown and overexpression of fat mass and obesity-associated protein (FTO). The results revealed that FTO negatively regulates PDC expression. This finding was corroborated in U87, U251, and A172 glioma cells via qRT-PCR and western blot analysis. Additionally, MTT and EdU assays revealed that PDC overexpression inhibited cell proliferation, while PDC knockdown accelerated it. Moreover, the proliferation-enhancing effect of FTO overexpression was reduced by PDC overexpression, and the proliferation-inhibiting effect of FTO knockdown was reversed by PDC knockdown. These findings suggest that PDC serves as a functional target of FTO. Furthermore, PDC enhanced the antitumor efficacy of temozolomide (TMZ). In summary, this study demonstrates for the first time that PDC plays a crucial role in regulating cell proliferation and TMZ sensitivity in glioma cells, providing a potential therapeutic target to improve treatment outcomes for the patients with glioma.