Bone cement is a promising substitute for bone repair due to its simple operation, excellent plasticity and self-setting after filling bone defect by injection. In this study, calcium sulfate hydrate (CSH)/mesoporous bioglass (MBG) bone cements were prepared through changing the MBG incorporation amount. The ratio of liquid to powder (RLP), mechanical strength, in vitro bioactivity, degradation and cell responses on CSH/MBG cements were investigated. The results showed that appropriate setting times for CSH/MBG cements could be achieved by adjusting the RLP, and the compressive strength was in the range of 5–16MPa. Also, CSH/MBG cements had excellent apatite mineralization ability, and the MBG incorporation could regulate the degradation rate. Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured on CSH/MBG cements, and the results indicated that CSH/MBG cements stimulated cell proliferation and differentiation. Furthermore, CSH/MBG cements had a sustained drug release property for use in local drug delivery therapy. Hence, CSH/MBG cements have more potential to be bone substitute for bone repair.