Enterococcus faecalis is a gram-positive bacteria that, while a frequent gut commensal, is one of the leading causes of nosocomial infections, which comprise urinary tract infections, endocarditis, bacteremia and meningitis. An important clinical feature of this species is the resistance to a wide range of antimicrobial agents, as demonstrated in clinical, food and water isolates. It not only contains several natural antibiotic resistances, but it is also capable of acquiring new ones as a result of
mutations or by acquisition of new genes. Thus, there is a continuous need to search for new drugs that may be used against E. faecalis. Some naturally occurring chemical compounds have played a central role in antibiotic drug discovery, with a very significant percentage of clinically proven drugs being derived from natural products. Recently, studies have been reporting that even commonly used herbs, fruits or vegetables, may contain molecules that could constitute potential new treatment against several bacterial infections, including multi-drug resistant bacteria. The present chapter focuses on the most recent published reports on naturally-derived antimicrobial molecules effective against E. faecalis. When available, the molecular mechanism of action will also be addressed.