Cyclocarya paliurus (Batal.) Iljinsk (C. paliurus) is a well-known medicinal plant in China for regulating blood glucose of diabetic and is commonly called ‘sweet tea tree’. The aim of this study was to optimize the extraction condition using L9(3)4 orthogonal experimental design by reflux extraction and investigate the antioxidant activity of polysaccharides from C. paliurus. Four factors and three levels each factor were designed to determine the optimum parameters for the extraction and the total reducing power determination was used to study the antioxidation of the polysaccharides from C. paliurus. The results showed that the optimum extraction time was 2.5 h, times were 2, temperature was 90 °C and material/solvent ratio was 1:15 (g/mL). Under this condition, maximum yields of 4.95% could be obtained. The reducing power test confirmed the antioxidant activity of polysaccharides from C. paliurus. In summary, reflux extraction is a good, simple and efficient method for the extraction of polysaccharides from C. paliurus and the polysaccharides possess an antioxidant activity.