This study analyzes and evaluates the use of cellulose nanocrystals (CNCs), stiff nanosized natural materials that have been modified to mimic heparin. These CNCs are simple polysaccharides with a similar backbone structure to heparin, which when modified reduces coagulation and potentially the long-term effects of solution-based anticoagulants. Thus, CNCs represent an ideal foundation for generating materials biocompatible with blood. In this study, we developed a biocompatible material that inhibits blood clotting through surface functionalization to mimic heparin. Surface chemistry of CNCs was modified from "plain" CNCs (70 mmol SO3-/kg) to 500 mmol COO-/kg (TEMPO-oxidized CNCs) and 330 mmol SO3-/kg CNCs (sulfonated CNCs). Platelet adherence and blood assays show that changes in functionalization reduce coagulation. By utilizing and modifying CNCs reactive functional groups, we create a material with unique and favorable mechanical properties while also reducing clotting.