| Osteoporosis (OP) is a systemic metabolic bone disease characterized by decreased bone mass, degradation of bone microarchitecture, and increased bone fragility. Its pathogenesis involves a dynamic imbalance between osteogenesis and bone resorption. Icariside II (ICS II), the main active ingredient of Epimedium, has shown significant potential in the treatment of OP due to its multi-target and multi-level mechanisms of action. This paper reviews recent advancements in ICS II research since the past five years, focusing on its pharmacological effects, including regulating osteogenic differentiation via MAPK/ERK, Wnt/β-catenin, and EGFR-Akt-Nrf2 signaling pathways, inhibiting osteoclast activity, and improving bone metabolic balance. Furthermore, this review discusses strategies to enhance the bioavailability of ICS II, such as nanotechnology, phospholipid complexes, and exosome-based drug delivery systems, addressing challenges associated with its poor solubility and low bioavailability. Despite promising findings from in vitro and in vivo studies, further exploration is needed to assess the long-term safety and clinical applicability of ICS II. |