AimsThe study aimed to assess whether violacein has antimicrobial activity on Staphylococcus epidermidis and synergistically modulates the action of commercially available antimicrobial drugs. Methods and ResultsViolacein showed excellent antimicrobial activity on biofilm-forming and nonbiofilm-forming S. epidermidis strains (ATCC 35984) (ATCC 12228), with bacteriostatic (MIC=20gml(-1) and 10gml(-1) respectively) and bactericidal effects (MBC=20gml(-1) for both strains), observed in short periods of exposure. The violacein bactericidal concentration led to S. epidermidis death after 2-3h of exposure. Additionally, violacein synergistically modulated the activity of different antimicrobial classes on S. epidermidis ATCC 12228 (818%; n=9) and on S. epidermidis ATCC 35984 (545%; n=6), reducing the MIC of these antibiotics by up to 16-fold. ConclusionViolacein shows excellent antimicrobial activity on S. epidermidis strains. Significance and Impact of the StudyViolacein shows the potential for the development of a new drug for the treatment of infections caused by S. epidermidis.