LACTB, a mitochondrial protein, was ubiquitously expressed in different mammalian tissues, such as liver, heart, and skeletal muscle. It has been shown that LACTB is downexpressed in breast cancers, and it suppresses the proliferation and promotes the apoptosis of breast cancers. However, its role in the progression and prognosis of glioma remains unknown. In this study, we analyzed the clinicopathological features and outcomes of LACTB expression in 98 glioma patients and investigated the effects of LACTB overexpression on the proliferation, invasion, and angiogenesis of glioma cells in vitro. We observed a significant decrease in LACTB expression in glioma, and downexpression of LACTB is correlated with a poor prognosis of glioma patients. Moreover, Cox regression analysis reveals that the LACTB is an independent prognostic indicator for glioma patients. Overexpression of LACTB could suppress the proliferation, invasion, and angiogenesis of glioma cells. In addition, overexpression of LACTB could inhibit the expression of PCNA, MMP2, MMP9, and VEGF. Taken together, these data indicate that LACTB may serve as a promising therapeutic target for gliomas.