Abstract: Nanocellulose, which exhibits exceptional mechanical strength, high specific surface area, remarkable biocompatibility, and versatile surface chemistry, has emerged as a promising biomaterial platform. This review provides a comprehensive overview of the preparation methods, surface modification strategies, and composite engineering approaches for cellulose nanocrystals (CNCs), cellulose nanofibers (CNFs), and bacterial cellulose (BC). Particular attention is given to their distinct application strategies and recent advances in tissue engineering, smart/responsive drug delivery, wound dressings and hemostasis, and biosensing. We further propose a structure–property–function framework structured along the logical continuum of “modification strategy → physicochemical changes → biological performance → application scenario”. This framework systematically introduces how surface chemical modifications govern key properties such as dispersibility, interfacial compatibility, and environmental responsiveness, and highlights how the differentiated application advantages of CNCs, CNFs, and BC emerge from their inherent differences in morphology, dimensions, crystallinity, and surface charge characteristics. In addition, this review outlines several critical challenges impede clinical translation, including high production costs, insufficient batch-to-batch reproducibility, and the absence of standardized safety assessment systems. Looking forward, the development of green and scalable manufacturing processes, construction of multifunctional integrated platforms, and establishment of robust safety evaluation protocols will be essential. This review aims to provide a strategic roadmap for advancing nanocellulose-based composites toward biomedical applications and eventual clinical practice.