Chitosan oligosaccharide (COS) and kojic acid (KA) were used as synthetic initiators and the COS-based polymer (COS-O-KA) were synthesized by selective partial alkylation reaction to graft kojic acid onto the COS molecular chain. After characterization of structure by NMR spectroscopy, molecular weight, polydispersity index, water-solubility, hemolysis assay in vitro, biocompatibility in vitro, antioxidant activity, and animal toxicity of COS-O-KA were studied. The results revealed that the three polymers of different substitution degree (COS-O-KA1-3) were synthesized successfully which proved by NMR spectroscopy. In addition, COS-O-KA1-3 exhibited preferable water-solubility, hemolytic activity in vitro, biocompatibility in vitro, and scavenging activity of DPPH free radical and ABTS⁺ free radical in comparison with that of the free COS and KA. Among them, when the concentration was 15mg/mL, the hemolysis rate of COS-O-KA1-3 was less than 20%, while the hemolysis activity of the same concentration of COS and KA was more than 30%. The DPPH free radical scavenging rates of COS, KA, COS-O-KA1, COS-O-KA2 and COS-O-KA3 were 52.28%, 59.33%, 85.21%, 87.35% and 82.83%, respectively. The scavenging activity of COS-O-KA1-3 on ABTS+ free radical increased slowly and reached a stable level (83.87%, 85.76%, 82.33%, respectively) at 2.0mg/mL, which was much higher than that of COS (39.65%) and KA (46.54%). Meanwhile, owing to its non-cytotoxicity, COS-O-KA might be considered as a promising material for antioxidant applications.