Typically, bone regenerative medicine is applied to repair bone defects in patients with osteoporosis. Meanwhile, there is an urgent need to develop safe and cheap drugs that induce bone formation. Icariin, which is reported to promote the osteogenesis of stem cells in vitro, is the main active component of Herba Epimedii. However, whether icariin could repair bone defects caused by osteoporosis remains unknown. In this study, an osteoporosis model in rats was established by an ovariectomy first, and then, the osteogenic and angiogenic differentiation of bone mesenchymal stem cells (BMSCs) treated with icariin was evaluated. Furthermore, calcium phosphate cement (CPC) scaffolds loaded with icariin were constructed and then implanted into nude mice to determine the optimal construction. To evaluate its osteogenic and angiogenic ability in vivo, this construction was applied to calvarial defect of the ovariectomized (OVX) rats accompanied with an icariin gavage. This demonstrated that icariin could up-regulate the expression of osteogenic and angiogenic genes in BMSCs. Meanwhile, osteoclast formation was inhibited. Moreover, CPC could act as a suitable icariin delivery system for repairing bone defects by enhancing osteogenesis and angiogenesis, while the systemic administration of icariin has an antiosteoporotic effect that promotes bone defect repair.