Squid skins are one kind of byproducts during the processing; some of them are used as feedstuff or fertilizer, but with low economic value. In order to utilize the squid skins completely, the extraction methods and functional properties were investigated. In proximate analysis showed that crude protein was the mainly composition in squid skin and accounts for 70.6% of a dry weight basis. The predominant free amino acids (FAAs) of squid skin were glycine, proline and hydroxyproline, which amounted to 53.1% of total FAAs. Squid skin hydrolysate was prepared by an enzymatic hydrolysis with commercial protease, which contained 80.97% peptides with the molecular weight less than 3000 Da. Further, the hydrolysates exhibited strong antioxidant abilities, including DPPH free radical scavenging activity, chelating activity of Fe2+, reducing power, and SOD activity, the valves were 86.76%, 95.42%, 2.63 and 98.80%, respectively. Furthermore, the hydrolysates were safety, that demonstrated by the acute toxicity test with a daily dose of 15 g/kg body weight for consecutive 14 days. Moreover, the hydrolysates could not only exhibit blood pressure regulation by against the angiotensin I-converting enzyme, but also could prevent H2O2-induced cytotoxicity, which was well reflected in the elevation of SOD (superoxide dimutase) activity. In addition, the fibrinolytic enzyme activity from squid skin with Bacillus natto N1 and N3 after 96hr fermentation appeared 10.00 FU/mL and 10.90 FU/mL, respectively. These fermented products were also shown the high angiotensin I-converting enzyme inhibitory activity and accounted for 91.98 % (N1) and 90.35% (N3). Summary results indicated the potential of the hydrolysate or fermented products from squid skin could be used as a novel candidate for antioxidant, blood pressure regulatory and fibrinolytic agents on the functional foods or supplementary. Therefore, optimal utilization of this under-utilized squid skin, especially the production of value-added products, is a promising means to increase the revenue of producers.