Based on the concept of green and environmental protection, peel waste of Punica granatum was taken as the research object to carry out the process of pomegranate peel extract (PPE), with natural deep eutectic solvent (NADES) as the extraction solvent, and ultrasonic-assisted extraction (UAE) method as the extraction method. 17 kinds of solvents were prepared for solvent screening, and choline chloride-ethylene glycol with a molar ratio of 1:2 and moisture content of 30%, i.e., ChEG-30, was optimal for PPE and was the first time to be utilized for natural product extracts as the best solvent, especially for polyphenol extracts until now. Based on ChEG-30, through single-factor and response surface methodology (RSM) experiments, optimal UAE parameters were determined: ultrasonic time of 19 min, material liquid ratio of 36:1 mg/mL, ultrasonic power of 284 W, and ultrasonic temperature of 70 degrees C. Furthermore, ChEG-30 had more advantages in terms of total phenolic content (TPC), punicalagin content (PgC), as well as antioxidant abilities than traditional solvents. In conclusion, ChEG-30 was optimized for PPE for the first time, and the UAE process of pomegranate peel by using ChEG-30 was systematically developed, which laid a certain research basis for possible subsequent green industrial scale-up applications.