Cellulose nanocrystals (CNCs) have been modified through surface graft polymerization of (l)-lactide for the purpose of improving dispersion and reducing aggregation of CNCs into chloroprene rubber (CR). Statistically designed experiments have been carried out to study the effects of polymerization conditions (temperature, and catalyst and monomer concentrations) on water contact angle, solvent dispersibility, and particle size distribution of the produced mCNCs. The effects of catalyst concentration and interaction of monomer-catalyst concentrations were found to be significant. Dry films produced from mCNCs exhibited surface hydrophobicity as evidenced by very high water contact angles (> 90°). In addition, mCNCs in powder form exhibited very good water/latex dispersibility. Blending of mCNCs with CR latex resulted in well-dispersed modified CNC/CR composites based on microscopy observations. The tensile properties of cast films produced from CNC/CR and mCNC/CR composites have been evaluated and it has been found that increasing the CNC and mCNC content increases tensile strength and modulus while maintaining elongation at break close to that of the unfilled CR. Composites containing 3 wt% of mCNCs exhibited the best properties with tensile strength and modulus improving by about 200% and 450%, respectively. These results are very promising and suggest that these mCNC/CR composites could find applications in the manufacturing of cut/fat resistant medical gloves, balloons, catheters, and other biomedical devices.