The tilapia (Oreochromis niloticus) skin hydrolysate was produced by thermal or enzymatic hydrolysis processes. Several product characteristics were studied such as the average molecular weight, 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity, yield, and protein content, in order to compare thermal hydrolysis and enzymatic proteolysis processes for the hydrolysed tilapia skin collagen production. The effects of the following hydrolysis parameters (retorting time and pH, protease combination, and proteolysis time) were studied. Compared with the thermal hydrolysis process, the enzymatic proteolysis process needed less time and milder conditions, under which hydrolysates could be obtained as low molecular weight antioxidant peptides.