Metalloproteinase or metalloprotease is a protease enzyme whose catalytic mechanism involves a metal (zinc or cobalt). It is the most diverse type of protease, with more than 50 families classified. The metal ion is interacted with the protein via three ligands which consist of histidine, glutamate, aspartate, lysine, and arginine. There is another binding site in the metalloproteinase that is absorbed by the unstable water molecules. Exopeptidases and endopeptidases, including ADAM proteins and matrix metalloproteinases, are two kinds of well-known metalloproteases. EDTA (metal chelator removing zinc) and orthophenanthroline are two main chelating agents that can lead to complete inactivated metalloproteases. Mounting evidence supports that metalloproteases play an important role in many physiological processes, including tumor tumorigenesis and tumor progression, chronic venous disease and muscle damage.