Throughout the last two decades, cellulose, as the most available green and nontoxic biomacromolecule, has gained increasing interests in any form of nanostructures owing to its superior characteristics consisting of high crystallinity, high specific surface area, surface chemical reactivity, amphiphilic nature, high aspect ratio, stiffness, excellent thermal stability, better mechanical properties, nontoxicity, easy processing renewability, biodegradability, and biocompatibility. The presence of hydroxyl functional groups eases the functionalization process through chemical, physical, and biological reactions, bringing about the enhancement of a variety of nanomaterials with a tunable structure which builds up new opportunities in terms of nanomaterial fabrication. Moreover, many structures of nanocelluloses (NCs), such as cellulose crystallites, nanocrystalline cellulose, nanorods, nanowires, nanoplatelets, nanoyarns, nanospheres, and cellulose nanowhiskers, can be prepared over various industrialized methodologies using a broad range of applications. In this chapter, the latest advances in the synthesis, functionalization, and promising biomedical applications of spherical cellulose nanomaterials were described and elaborated. It was started with a brief background of cellulose, its structural association, and also classification of cellulose nanomaterials for beginners in this field. Afterward, diverse experimental processes for the fabrication of cellulose nanospheres, their characteristics, and characterization techniques were discussed. Moreover, recent and emerging applications of spherical cellulose nanoparticlesin biomedical were presented.