The macrophage-dominated bone immune response plays an important role in osteogenesis of bone defects. Generally, M2 macrophages are beneficial to promote osteogenesis. However, recent studies have confirmed that M1 also plays an important role in early angiogenesis, osteointegration. Therefore, achieving sequential polarization of macrophages from M1 to M2 may be more beneficial for osteogenesis. In this study, a new type of bone immunomodulatory IFN-γ/Sr-dropped bioactive glass composite scaffold (IFN-γ/SrBG) was successfully prepared which integrates multiple biological functions at different stages of the bone healing process. The scaffold can polarize macrophages into pro-inflammatory M1 type at the early stage of implantation by releasing IFN-γ within the first day, and then polarize macrophages into anti-inflammatory M2 type at a later stage by releasing Sr2+ from SrBG, which promoted mature bone formation in bone defects to a greater extent. Therefore, IFN-γ/SrBG scaffolds are expected to become excellent bone tissue engineering materials by sequential regulation of macrophage polarization.