© 2014 Association of Food Scientists & Technologists (India) Fish skin, a by-product from fish processing industries, still contains a significant amount of protein-rich material. Gelatin was extracted from Nile tilapia skin with the yield 20.77 ± 0.80 % wet weight. Gelatin was then separately hydrolyzed by proteases, including bromelain, papain, trypsin, flavourzyme, alcalase and neutrase. Low molecular weight gelatin hydrolysate (<10 kDa) has a great potential as an antioxidant agent. Flavourzyme hydrolysate has potent activity on ABTS radical scavenging (1,413.61 ± 88.74 μg trolox/mg protein) and also inhibits the oxidation of linoleic acid at a high level (59.74 ± 16.57 % inhibition). The greatest reducing power is in alcalase hydrolysate (4.951 ± 1.577 mM trolox/mg protein). While, bromelain hydrolysate has the highest ferrous ion chelating activity (86.895 ± 0.061 %). Evaluation of the angiotensin-I-converting enzyme’s inhibitory activity indicates that all hydrolysates have great potency as an antihypertensive agent. All studied tilapia skin gelatin hydrolysates contain potent antioxidant and anti-hypertensive effects.