Bioactive peptides were produced from sericin, a by-product from silk industry wastewater, by using Protease P. The optimal hydrolysis conditions (pH of 8.40, temperature of 43.97 °C and the enzyme/substrate ratio of 3:100) were estimated by using response surface methodology with a maximum degree of hydrolysis of 14.43% and the minimum IC 50 value for the ferrous ion-chelating activity of 0.128 mg/mL. The freeze-dried sericin hydrolysate (SH), produced by using Protease P and under the above optimal conditions, contained 82% of crude protein, 13% of moisture and 5% of ash. The physiochemical analysis shows that the amino acids with hydroxyl groups (Ser and Thr) of SH accounted for 30% or so, and SH was a mixture of hydrophilic peptides mostly distributed among 250–4000 Da. SH exhibited excellent antioxidant activities in two measurements, including the ferrous ion-chelating activity and the reducing power. Moreover, SH also exhibited a notable tyrosinase-inhibitory effect in a dose-dependent manner. This study firstly showed an effective bioprocess for the production of sericin bioactive peptides, which may be used as valuable ingredients in the food, cosmetic and medicine industries.