Glioma is a common primary intracranial tumor. Malignant glioma has a high mortality rate and an inferior prognosis. Despite various therapeutic interventions, the overall survival rate is still meager. Sesquiterpene lactone is a kind of natural product containing α-methylene-γ-lactone, which has strong anti-tumor activity. In recent years, there have been many reports on the anti-glioma effect of sesquiterpene lactone compounds, such as ACT001, which is a structural modification of sesquiterpene lactone (Parthenolide) and has entered the clinical trial stage as a potential anticancer drug. This paper reviews the activity and mechanism of sesquiterpene lactones with anti-glioma effects, which have been studied in recent years.