Biocompatible polymer nanocomposites represent a rapidly advancing class of materials with significant potential in biomedical and healthcare applications. By integrating biocompatible polymers with functional nanofillers, these materials offer unique combinations of mechanical strength, bioactivity, and controlled degradation tailored to specific physiological environments. This chapter provides a comprehensive overview of biocompatible polymer nanocomposites, covering the fundamentals of biocompatibility, selection of suitable natural and synthetic polymers, and various types of nanofillers such as carbon-based materials, metal oxides, and bioceramics. Emphasis is placed on fabrication techniques—including electrospinning, solvent casting, and 3D printing and how they influence material structure, performance, and biological interactions. The chapter further explores the wide range of biomedical applications, including tissue engineering scaffolds, drug delivery systems, wound-healing materials, biosensors, and implantable devices. Key aspects of toxicology, immunogenicity, and biological safety are critically reviewed, along with current strategies for evaluating in vitro and in vivo biocompatibility. Additionally, the chapter addresses regulatory considerations, clinical translation challenges, and ethical implications surrounding the use of nanocomposites in healthcare, by highlighting recent advancements and emerging trends such as smart, responsive, and bioresorbable systems. This chapter underscores the transformative potential of biocompatible polymer nanocomposites in next-generation medical technologies. It concludes by outlining current limitations and future research directions aimed at overcoming challenges in scalability, reproducibility, and long-term safety.