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Nanocrystalline cellulose is a renewable nanomaterial that has gained huge attention for its use in various applications from advanced biomedical material to food packaging material due to its exceptional physical and biological properties, such as high crystallinity degree, large specific surface area, high aspect ratio, high thermal resistance, good mechanical properties, abundance of surface hydroxyl groups, low toxicity, biodegradability, and biocompatibility. However, they still have drawbacks:(1) sources of raw materials and its utilization in the production of nanocomposites and (2) high chemical and energy consumption regarding the isolation of macro-sized fibers to nano-sized fibers. The incorporation of hydrophilic nanocrystalline cellulose within hydrophobic polymer limits the dispersion of nano-sized fibers, thus resulting in low mechanical properties of nanocomposites. Hence, surface modification on nano-sized fiber could be a solution to this problem. This review focuses on the advanced developments in pretreatment, nanocrystalline production and modifications, and its application in food packaging, biomedical materials, pharmaceutical, substitution biomaterials, drug excipient, drug delivery automotive, and nanopaper applications.