Extraction of polyphenolic compounds from African nutmeg (Monodora myristica (Gaertn.)) peels using natural acidic deep eutectic solvents coupled to ultrasound-assisted extraction (NADESs-UAE) followed many factors at a time (MFAT) screening with response surface optimization was investigated. Fourteen different NADESs based on citric acid as hydrogen bond acceptor (HBA) were designed and tested. Sucrose, fructose, xylitol, glycerol, glycine, and glucose were used as hydrogen bond donors (HBDs). The responses studied are total phenolic compounds (TPC), total flavonoid compounds (TFC), and antioxidant activity (AA) based on cupric ion reducing antioxidant capacity (CUPRAC) and ferric reducing antioxidant power (FRAP). The UAE procedure was optimized with the most efficient NADES. Quadratic models produced satisfactory fitting of the experimental data regarding TPC (R