Cellulose nanocrystals (CNCs) are renewable nanosized materials with exceptional physicochemical properties that continue to garner a high level of attention in both industry and academia for their potential high-end material applications. These rod-shaped CNCs are appealing due to their non-toxic, carbohydrate-based chemical structure, large surface area, and the presence of ample surface hydroxyl groups for chemical surface modifications. CNCs, generally prepared from sulfuric acid-mediated hydrolysis of native cellulose, display an anionic surface that has been exploited for a number of applications. However, several recent studies showed the importance of CNCs' surface charge reversal towards the design of functional cationic CNCs. Cationization of CNCs could further open up other innovative applications, in particular, bioapplications such as gene and drug delivery, vaccine adjuvants, and tissue engineering. This mini-review focuses mainly on the recent covalent synthetic methods for the design and fabrication of cationic CNCs as well as their potential bioapplications.