Commercial bone substitute, such as calcined bovine bone (CBB), is currently extensively used as an alternative to autogenous bone. However, CBB lacks osteoinductivity and merely serves as a scaffold for native bone formation. To address this issue, we designed and prepared a heptaglutamate (E7)‐modified BMP2‐mimicking peptide (7E) and carried out a series of comprehensive physical characterizations and in vivo and in vitro studies to evaluate its role in the repair of cranial defects. The data elucidated that the amount of peptide anchoring to the bone graft materials was remarkably increased after modified with E7. Of note, 7E had a relatively stable and durable release, which promoted the osteogenic differentiation of rat derived bone marrow mesenchymal stem cells (BMSCs) and enhanced the bone regeneration of a rabbit calvarial defect by regulating the expression of the Runx2/SP7 axis. In summary, the composite biomaterials incorporating the E7‐modified BMP2‐mimicking peptide and CBB prepared in this study is a novel bone augmentation material with the merits of non‐immunotoxicity, convenience, and low cost. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:80–93, 2020.