Organic-inorganic hybrid materials are multifunctional composites that combine distinct organic and inorganic components to yield synergistic enhancements in properties such as mechanical strength and piezoelectric performance, resulting in performance that exceeds that of the individual materials. This review begins by examining organic-inorganic hybrid structures found in nature, particularly within biological systems, and highlights the historical development of synthetic hybrids inspired by these natural designs. These materials are categorized based on their dimensional architectures, ranging from zero-dimensional (0D) to three-dimensional (3D) systems. A focused discussion follows on the mechanisms through which the organic and inorganic phases interact to influence the mechanical and piezoelectric properties, with a particular emphasis on interfacial interactions, structural hierarchy, and functional tunability. The biomedical applications of these hybrid materials are then summarized, detailing their roles in biomechanical energy harvesting, sensing, and regenerative medicine. This review concludes by addressing emerging challenges and outlining future directions for the rational design of organic-inorganic hybrid materials to advance biomedical technologies.