The efficient extraction of natural products from biomass is deemed an essential area of interest using green technology in the pharmaceutical and biochemical industries. In recent years, deep eutectic solvents (DESs) have been paying broad interest as compatible, safe, and inexpensive solvents. In this study, we addressed, for the first time, to give a fruitful illustration to extract bioactive compounds from favourite Lycium barbarum L. fruits using DESs as green designer solvents, and displaying the tuneability of DESs to extract bioactive compounds from biomass efficiently. Among the studied DESs, the 1 : 2 M mixture of choline chloride and p-toluene sulfonic acid (DESs-6) with an ultra-sound assisted extraction (UAE) method was more efficient to get high extraction yields of flavonoids including myricetin (57.2 mg/g), morin (12.7 mg/g), and rutin (9.1 mg/g) in net DESs. The resulting extraction method in which 50 mg of sample powder was extracted by UAE for 1.5 h using DESs-6 was found to be a more efficient process than conventional extraction methods such as heating plus stirring. Operational conditions including the extractant to sample solid ratio, the effect of water content, the effect of temperature, recycling of DESs, and the effect of ultra-sound irradiation time were investigated. The proposed DESs based extraction procedure attained recovery for flavonoids were in the range 75.6%-96.9%. Therefore, p-toluenesulfonic acid-based DESs may have strong potential as promising materials for the green and efficient extraction of pharmaceutical compounds from other plants or fruits.