Background: Hesperidin is a natural product and a strong antioxidant with potential applications in various food and pharmaceutical products. However, its poor water solubility greatly limits its applications. Results: In this study, chitooligosaccharide (COS) was applied to prepare a stable complex with hesperidin (Hesp-COS) via the spray-drying method at 100°C for 20min. The resultant complex was characterized by Fourier transformation infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy and proton nuclear magnetic resonance spectroscopy. It was demonstrated that the aromatic rings of hesperidin interacted with COS through hydrogen bonding and formed Hesp-COS complex. As a result, both the water solubility and antioxidant activity of Hesp-COS were higher than that of the free hesperidin. Conclusion: The preparation conditions of Hesp-COS in this study were efficient and produced an increment in both the water solubility and antioxidant activity of hesperidin.