The treatment of glioblastoma, and other types of brain cancer, is limited due to the poor transport of drugs across the blood brain barrier and poor penetration of the blood-brain-tumor barrier. In the present study, cyclic Arginine-Glycine-Aspartic acid-D-Tyrosine-Lysine [c(RGDyK)], that has a high binding affinity to integrin v3 receptors, that are overexpressed in glioblastoma cancers, was employed as a novel approach to target cancer by delivering therapeutic molecules intracellularly. The c(RGDyK)/docetaxel polylactic acid-polyethylene glycol (DTX-PLA-PEG) micelle was prepared and characterized for various in vitro and in vivo parameters. The specific binding affinity of the Arginine-Glycine-Aspartic acid (RGD) micelles, to the integrin receptor, enhanced the intracellular accumulation of DTX, and markedly increased its cytotoxic efficacy. The effect of microtubule stabilization was evident in the inhibition of glioma spheroid volume. Upon intravenous administration, c(RGDyK)/DTX-PLA-PEG showed enhanced accumulation in brain tumor tissues through active internalization, whereas non-targeted micelles showed limited transport ability. Furthermore, RGD-linked micelles showed marked anti-glioma activity in U87MG malignant glioma tumor xenografts, and significantly suppressed the growth of tumors without signs of systemic toxicity. In conclusion, the results of the present study suggest that ligand-mediated drug delivery may improve the efficacy of brain cancer chemotherapy.