In order to determine the optimal conditions for the extraction of polyphenols from Dendrobium huoshanense by ultrasonic-assisted cellulase, response surface methodology was used to optimize the extraction process. Antioxidant activity of Dendrobium huoshanense polyphenols was evaluated. The results showed that the optimal conditions for the extraction of polyphenols were as follows: ultrasonic power 180 W, ultrasonic time 20 min, cellulase concentra-tion 2.1 mg/mL, enzymolysis temperature 57 ℃, enzymolysis time 71 min, and enzymolysis pH 5. Under these conditions, the average yield of polyphenols was 13.74 mg/g. Antioxidant assays revealed that Dendrobium huoshanense polyphenols had significant antioxidant activity. DPPH and ABTS radical scavenging activities had a stronger relationship with the content of polyphenols, and their hemi-inhibitory concentrations (IC₅₀) were 0.057 and 0.027 mg/mL, respectively.