<![CDATA[Background: Bone disorders, such as osteoporosis and inflammatory osteolysis, require regenerative therapies with improved safety and multimodal mechanisms. Marine natural products (MNPs) provide diverse chemical scaffolds with potential anabolic and antiresorptive actions; however, the synthesis of preclinical evidence and translational appraisal remains limited. Objective: To systematically synthesize preclinical evidence on the effects and molecular mechanisms of MNPs on bone, with emphasis on exemplar compounds (phorbaketal A and largazole) and translational considerations. Methods: The review process followed a PRISMA-based systematic literature review approach, including screening, data extraction, study quality evaluation, and thematic synthesis based on the identified molecular pathways. Results: Convergent pathways included inhibition of RANKL-RANK, NFATc1, and NF‑κB signaling, modulation of MAPKs (ERK/JNK), and activation of Wnt/β‑catenin and Runx2‑dependent osteogenic programs. Some compounds, such as phorbaketal A and largazole, showed dual-action potential in osteoblasts and osteoclasts. These effects were demonstrated in both bone cell cultures and animal models, yielding statistically significant results in both. Conclusion: Marine products are potential sources of bone therapeutic agents with multi-target mechanisms. This synthesis provides a conceptual foundation for the development of novel therapeutics based on marine biodiversity, promoting translational research toward clinical applications, and regulatory foresight will accelerate responsible translation of promising candidates like phorbaketal A and largazole,]]>
