In this study, glucose transporter and folic acid (FA) receptor-mediated Pluronic P105 polymeric micelles loaded with DOX (GF-DOX) were prepared for enhancing the blood-brain barrier (BBB) transportation and improving the drug accumulation in the glioma cells. The pH-triggered DOX release of GF-DOX indicating a comparatively fast drug release at weak acidic condition and stable state of the carrier at physiological environment. The transport of GF-DOX across the in vitro BBB model showed that GF-DOX exhibited higher BBB transportation ability with the transporting ratio of 21.47% in 4 h. The carrier was internalized into C6 glioma cells upon crossing the BBB model for the combined effect of the brain targeting by transportation of glucose transporter and active tumor cell targeting by FA receptor-mediated endocytosis. Moreover, minimized weight changes and high suppression ratio of tumor growth were observed after intravenous injection of GF-DOX. In conclusion, the glucose transporter and FA dual-targeting micelles would provide a safe and effective strategy for new modalities to treat brain tumor.