Abstract: In the present study, response surface methodology was used to optimize the conditions for ultra-high pressure (UHP) extraction of polyphenols from Lonicera caerulea fruits and a comparison was performed with ultrasonic-assisted extraction (UAE) with respect to extraction efficiency, processing conditions and antioxidant activity of polyphenols. The results showed that the optimal conditions for UHP-assisted extraction that provided the maximum yield of polyphenols of (778.23 ± 3.45) mg/100 g berries were determined as follows: 50% ethanol as the extraction solvent, a solid-to-liquid ratio of 1:19 (g/mL), an extraction temperature of 30 ℃, an extraction pressure of 406 MPa, and an extraction time of 11.5 min. The optimal conditions for ultrasonic-assisted extraction that gave the maximum yield of polyphenols of (785.74 ± 3.89) mg/100 g berries were determined to be 50% ethanol as the extraction solvent, a solid-to-liquid ratio of 1:25 (g/mL), an extraction temperature of 40 ℃, an ultrasonic power of 500 W, and an extraction time of 90 min. Antioxidant test results showed that the antioxidant activity of polyphenols from ultra-high pressure extraction was significantly higher in terms of 2,2’-azinobis( 3-ehtylbenzothiazoline-6-sulfonic acid) diammonium salt radical (ABTS+·) scavenging capacity, ferric reducing antioxidant power (FRAP), and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity when compared with those from ultrasonic extraction and VC at the same concentration levels. Although the ultra-high pressure extraction took a shorter time and yielded polyphenols with higher antioxidant activity, its efficiency in large-scale extraction of polyphenols was not as good as that of the ultrasonic-assisted extraction due to the limitation in the size of the container used. Therefore, considering extraction yield and extraction efficiency, the ultrasonic-assisted extraction was better than the ultra-high pressure extraction for Lonicera caerulea fruit polyphenols.