Serum prolidase activity (SPA) plays a vital role in plaque stabilization in collagen turnover in atherosclerotic plaques. Thus, SPA has an essential role in the diagnosis and prevention of coronary artery disease. SPA values may be higher in hypertension, atrial fibrillation, coronary artery ectasia, and aneurysmatic diseases than average values due to collagen turnover and oxidative stress. We aimed to present a review to show the role of SPA based on cardiovascular diseases and how it will contribute to prognosis with the most recent data.