Ultrasound-assisted extraction (UAE) was applied as a pretreatment technique to improve the recovery of polyphenols from the almond hulls of four Tunisian and three Italian almond varieties, followed by the characterization with HPLC-DAD. The operating parameters (solid/liquid ratio, extraction time, and ethanol concentrations) were optimized using a Response Surface Methodology. A polynomial equation was calculated to describe the relationship between the operating parameters and dependent variables as total polyphenolic content (TPC) and antioxidant activity (RSA). A desirability function approach was used to determine the optimum conditions for operating parameters: a solid:solvent ratio of 2 g/100 mL, an extraction time of 13 min, and an ethanol concentration of 51.2%. Among the almond varieties, Pizzuta and Fakhfekh showed the highest polyphenol content and antioxidant activity. HPLC-DAD analysis of almond hull extracts confirmed that chlorogenic acid, catechin, and protocatechuic acid were the most important polyphenols in almond hull. The results highlighted that UAE could be an effective technique for the recovery of phenolic compounds from almond hull, thereby making this byproduct a promising source of compounds with potential applications in food and healthcare sectors.