Background: Dental caries is an infectious oral disease caused by cariogenic Streptococcus mutans. The streptococci inhabit dental-biofilms which comprise insoluble glucans. Objectives: To prevent dental caries, liposome-encapsulated nisin prepared from phosphatidylcholines with different acyl chain lengths were tested for bactericidal activity against cariogenic S. mutans. Materials and Methods: Liposomal nisins prepared from dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC), and distearoyl phoshatidylcholine (DSPC) were tested for their bactericidal activity against S. mutans 10449 and as a consequence, to inhibit the synthesis of insoluble glucan by the streptococci in vitro. Results: The bactericidal activities by minimum inhibitory concentration assay, DSPCnisin, DPPC-nisin, and DMPC-nisin were higher by factors of 10, 3.3, and 2.5 compared with unencapsulated nisin. Inhibition of glucan synthesis was sustained the longest by DSPC-nisin. On the release assay of these liposomes, nisin was released at the highest and lowest rates from DMPC-nisin and DSPC-nisin, respectively. The highest and most sustained levels of bactericidal activity correlated with the slow release of encapsulated nisin. Conclusion: The DSPC-nisin may be useful for preventing the formation of dental caries due to sustained release of nisin. Thus, prophylaxis with the liposomal nisin may serve to maintain oral health.