Biomaterials play a pivotal role in advancing regenerative medicine by enabling the restoration, replacement, or enhancement of tissue function. Their evolution spans from biologically inert substances to complex, bioactive, and biomimetic structures, making them essential in regenerative practices. Modern biomaterials, designed using bioactive and biocompatible components, provide environments conducive to cell attachment, proliferation, differentiation, and tissue regeneration by mimicking the extracellular matrix (ECM). Recent advancements in biomimetic natural biomaterials have improved ECM replication, which is critical for engineering tissue implants. Furthermore, mesenchymal stem cells (MSCs), with their multipotent properties and immunomodulatory capabilities, are frequently combined with biomaterials to enhance therapeutic outcomes. 3D bioprinting technology has emerged as a transformative tool for constructing functional tissue architectures, addressing the global shortage of organ donors—especially in cardiac and organ repair. Ongoing research continues to refine biomaterials to better support cell microenvironments, enhancing drug screening platforms and therapeutic performance. Despite rapid progress, challenges remain in material design, scalability, and clinical translation. This chapter provides an overview of the latest developments and hurdles in biomaterials for regenerative medicine, with a focus on their therapeutic potential in advancing tissue engineering and regenerative therapies.