The use of natural materials in regenerative orthopaedics has undergone significant evolution over many centuries. What began as the use of simple animal sinews and plant fibers for stabilizing fractures has now expanded into sophisticated biomaterials that are integral to modern regenerative medicine. Natural substances like collagen, silk fibroin, chitosan, and cellulose are now crucial in tissue engineering, providing innovative bone and cartilage regeneration solutions. Despite their promise, natural materials face challenges such as mechanical limitations, biodegradation rates, and immunogenicity. Additionally, advancements in 3D printing allow for the replacement of complex bone defects, particularly in trauma and tumour cases, but these remain non-biological solutions that lack permanent integration with host tissues. The emergence of hybrid materials—combining natural and synthetic components—offers new opportunities to enhance biomechanical properties and biocompatibility. Furthermore, emerging technologies such as gene editing and bioactive scaffolds are paving the way for more personalized and regenerative approaches. In this review paper, we will explore the historical progression of natural materials, their current applications, and the challenges that must be overcome to maximize their therapeutic potential in orthopaedic regenerative medicine. Ethical and sustainability considerations are also discussed. The review concludes with the authors’ vision for the future of the field.