Cardiovascular diseases(CVDs)are the leading global cause of mortality and disease burden.Statins are the most prescribed lipid-lowering drugs to treat hypercholesterolemia and prevent CVDs.The biochemical mechanism of statins consists of competitive inhibition of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase enzyme(HMG-CoAR),the limiting enzyme in cholesterol biosynthesis.Due to statin intolerance in some patient groups,the search for new inhibitors is a field of great interest.This review focusses on the studies reporting the inhibitory effect of protein hydrolysates and biopeptides on the HMG-CoAR enzyme activity.The analysis of the action mechanism and physicochemical characteristics of the HMG-CoAR inhibitory peptides revealed that the molecular weight,amino acid composition,charge,and polarity are key aspects of the interaction with the HMG-CoAR enzyme.In conclusion,this review reveals the potential of using food peptides as new cholesterol-lowering agents and opens a new interesting field of research.However,clinical approaches are mandatory to confirm their therapeutic hypercholesterolemic effect.