Phenolic compounds present in mango peel byproducts have been reported to have several beneficial health properties. In this study, we carried out an optimization of phenolic compounds using ultrasound-assisted extraction via ultrasonic bath and sonotrode. To optimize the variables of extraction, a Box–Behnken design was used to evaluate the best conditions to obtain high total phenolic compound extraction and high antioxidant activity evaluated by different methods (DPPH, ABTS, and FRAP). The optimal ultrasonic bath conditions were 45% ethanol, 60 min, and 1/450 ratio sample/solvent (w/v) whereas optimal sonotrode conditions were 55% ethanol, 18 min, and 65% amplitude. The extracts obtained at the optimal conditions were characterized by HPLC–ESI-TOF-MS. A total of 35 phenolic compounds were determined and, to our knowledge, several of them were tentatively identified for the first time in mango peel. The samples were composed mainly by phenolic acids derivatives, specifically of galloylglucose and methylgallate, which represented more than 50% of phenolic compounds of mango peel byproducts. In conclusion, sonotrode is a valuable green technology able to produce enriched phenolic compound extracts from mango peel byproducts that could be used for food, nutraceutical, and cosmeceutical applications.