<p>Bone regeneration remains a significant clinical challenge, particularly in cases of critical-sized defects and impaired healing conditions. Recent advances in tissue engineering have demonstrated the potential of bioactive natural compounds to improve the biological efficacy of bone scaffolds. This review examines the integration of natural medicinal compounds (NMCs), such as curcumin, resveratrol, berberine, 6-gingerol, and allicin, into scaffold designs for bone tissue regeneration. These compounds, derived from plants and other natural sources, exhibit osteoinductive, anti-inflammatory, antioxidant, and antimicrobial properties, making them promising agents for enhancing scaffold bioactivity. Various scaffold fabrication strategies are discussed, including incorporation through surface modification, encapsulation, and biomimetic mineralization. Furthermore, the review assesses contemporary in vitro and in vivo studies that illustrate enhanced osteogenesis, angiogenesis, and biocompatibility of these functionalized scaffolds. Issues including compound stability, release kinetics, and regulatory considerations are also examined. This review also examines factors influencing the osteogenic potential of natural compounds and highlights the combination of these compounds with other natural and synthetic agents as an emerging approach to improve bone regeneration outcomes. This review highlights the increasing potential of nature-inspired bone scaffold designs as an adjunct to conventional bone regeneration therapies.</p> Graphical Abstract <p></p>