Infective endocarditis is a serious infection occurring on the endothelial surfaces of the heart, especially at the valves. Oral commensal bacteria are the important etiologic agents in this disease. Common dental procedures, even non-surgical dental procedures, can often cause bacteremia of oral commensals. Periodontally diseased patients are at risk from bacteremia even after brushing the teeth. Bacteremia itself rarely affect healthy people but they can result in mortal infective endocarditis in those who have a predisposed risk for this disease, such as those with heart valve diseases, pacemaker implantation, etc. Infective endocarditis is thus established when all the 3 conditions are present simultaneously, i. e., 1) a predisposing impairments in the heart, 2) the introduction of bacteria into the bloodstream, and 3) the virulence of bacteria. Antibiotics have to be adequately used to prevent this infection, however, their frequent uses generates drug-resistant mutant bacteria, which is a serious social problem. The development of novel alternative drugs to be used instead of the current antibiotics is thus highly desired. We are now using several types of combinatorial peptide libraries to search for small size molecular mimetics that can interfere with the adhesion of bacteria to the target organ. The use of such peptides is expected to lead to the development of compounds for a novel preventive drug which does not kill bacteria, thus making it safer and less likely to generate drug-resistant mutants.