Genistein (GEN), a typical isoflavone compound, exhibits desirable pharmacological activities, such as antioxidation, anti-inflammatory, , and anti-cancer properties. However, the pharmaceutical application of GEN is limited because of its poor water solubility in aqueous systems. In this study, cellulose nanocrystals (CNCs) and cetyltrimethylammonium bromide (CTAB)-coated CNCs were used as carriers for GEN to improve its dissolution rate and antioxidant activity in aqueous systems. The CNC/GEN and CNC/CTAB/GEN nanocomposites were successfully prepared and characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, and X-ray diffraction analysis. The results showed that the nanonized GEN performed better and its crystalline structure decreased because of the formation of the CNC/GEN and CNC/CTAB/GEN nanocomposites. The GEN dissolution rates in the CNC/GEN and CNC/CTAB/GEN nanocomposites increased to 72.1% and 92.5% at 120 min, respectively, compared with that of the original GEN (0.85%). Furthermore, the in vitro antioxidant activity of the GEN, which was evaluated by the hydroxyl radical scavenging efficiency, was remarkably enhanced. Based on the above results, CNCs as nanocarriers are a useful method for improving the dissolution and antioxidant activities of GEN in aqueous system.