Extracellular vesicles (EVs) are small particles that mediate intercellular communications in local and distant microenvironments. Due to their ability to carry bioactive materials such as proteins, nucleic acids, and lipids, and to transfer their cargo into target cells, EVs are thought to be crucial mediators under pathological and physiological conditions. Recent investigations of their protein profiles have revealed the presence of metalloproteinases such as matrix metalloproteinases (MMPs) in EVs from various cell types and body fluids. Although information regarding the biological and clinical significance of MMPs in EVs is still limited, EV-associated MMPs can alter EV cargo by ectodomain shedding, exerting proteolytic activity following uptake by target cells, or directly contributing to degradation of extracellular matrix proteins surrounding cells. This review focuses on recent findings regarding EV-associated MMPs, and we further discuss their potential involvement in human diseases.