Bone is the most common organ affected by metastatic breast cancer. Targeting cancers within the bone remains a great challenge due to the inefficient delivery of therapeutic to bone. In order to increase the distribution of paclitaxel (PTX) in bone metastases, in this study, a novel bone-targeted glutamic oligopeptides-RGD peptide (Glu-RGD) derivative was designed and synthesized as liposome ligand for preparing liposome to effectively deliver PTX to bone metastases. The liposome was prepared and its particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis and cytotoxicity were also characterized. What's more, the Glu-RGD-Lip showed superior targeting ability in vitro and in vivo evaluation as compared to naked PTX, non-coated, singly-modified and co-modified by physical blending liposomes. All the results suggested that Glu-RGD-modified liposome showed excellent targeting activity to metastatic bone cancer. This study may be conducive to the field of bone-targeting drugs delivery.