Enzymatic hydrolysis of Blue shark skin using Protamex™ was evaluated seeking optimal process conditions. The influence of temperature (45 to 65 °C), pH (6.8 to 8), and enzyme/substrate ratio (E/S; 1% to 5%) on the responses of degree of hydrolysis and protein recovery were determined and process optimization was performed looking for maximum value of the responses. Optimum conditions were established (T = 51 °C, E/S = 4%, and pH = 7.1) and model validation was accomplished by triplicate. Under these conditions protein hydrolysates were prepared and characterized by their amino acid composition, peptide size distribution, and antioxidant capacity by ferric reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC) assays. A degree of hydrolysis of 19.3% and protein recovery of 90.3% were obtained at optimal conditions. Chemical score indicated that the hydrolysate supplies minimal essential amino acid requirements for adults. Molecular weight of peptides on the hydrolysate was below 6.5 kDa. Enzymatic hydrolysis process was efficient for recovery of low molecular weight peptides with important nutritional content and antioxidant activity (FRAP = 12 μmol eq. in FeSO(4).7H(2)O/g of protein, TEAC = 225.3 μmol eq. in trolox/g of protein).