Abstract: Glioma is the most common primary malignant brain tumor in the adult population, characterized by high incidence and low survival rates. Current standard treatment options exhibit limited efficacy. In recent years, the crucial role of cGAS-STING signaling in tumor immunity has garnered significant attention. This article systematically reviews the molecular mechanisms of cGAS-STING signaling in glioma and its potential tumor-suppressive effects, providing an in-depth exploration of various STING agonists and their delivery systems targeting this pathway. This review also summarizes the synergistic effects of combining cGAS-STING pathway activation with radiotherapy, chemotherapy, and immune checkpoint inhibitors, providing substantial references for the development of multimodal comprehensive treatment strategies.