This study investigated the impact of ultrasound (US) pretreatment on Alcalase and goat milk casein (GMC) to enhance GMC proteolysis. We assess the degree of hydrolysis (DH), TCA-soluble protein concentration, protein solubility and in vitro antioxidant activity. US pretreatment of Alcalase (40 °C/60 min) or GMC (60 °C/30 min) increased the relative enzyme activity by up to 15.6 and 18.1%, respectively. Hydrolysis using US pretreated samples increased the DH (up to 37%), and TCA-soluble protein concentration (up to 73%). This led to higher solubility (up to 37% at pH 4.0) and antioxidant activity (up to 37% in ABTS assay) of the hydrolysates after 180 min of reaction (p < 0.05). Our findings suggest Alcalase sonication as the best strategy to improve GMC proteolysis and the multifunctional properties of hydrolysates, due to the lower volume to be processed and performance similar to that observed after substrate sonication.