The fishing industry is responsible for the production of 196 million tons of fish and the consequent generation of waste (skin, viscera, bones, scales, heads, fins, etc.) which are generally discarded or transformed into products with low market value, such as flour of fish, fish oil, animal feed or fertilizer. These by-products, or residues, hold up to about 50% of the raw material's total weight and are potential sources of essential amino acids, collagen, gelatin, polyunsaturated lipids, and enzymes such as pepsin, trypsin, chymotrypsin, and collagenase proteases. In recent years the interest in marine proteins for the production of collagen peptides has increased, due to their bioactivity, biocompatibility, high bioavailability and safety. Thus, compound recovery is of great interest to different industries such as pharmaceuticals, food and nutraceuticals. Thus, this work aimed to produce collagen bioactive peptides extracted from the skin of Neotropical fish for possible biotechnological applications and a review on the subject. Various techniques for the recovery, identification and purification of enzymes capable of cleaving collagen molecules as peptide bonds and subsequently degrading them into small peptides from the residues have been used, such as the semi-purification technique of the aqueous two-phase system (SDFA). ) which was applied to the neglected residue (viscera) of Mullet (Mugil liza) for the treatment of enzymes with collagenolytic activity. In the two-phase aqueous PEG / citrate system, according to the 23 factorial design, using as variables Partition coefficient (K), Yield (Y), and Purification factor (FP) it was possible to observe that the extraction adjustments (Y ) ranged from 89 to 124.34% and from 242.11 to 435.61% for protease and proteases with collagenolytic activity, respectively. The results differentiated the advantage of this semi-purification technique with regard to the extraction and purification of collagenolytic enzymes with industrial application for the production of collagen peptides.