The aim of this study was to evaluate the antimicrobial effects of a newly developed anti-caries pH-sensitive controlled release system against Streptococcus mutans. For this purpose 9, 30, and 45 mg of NaF were placed in multilayer polymeric structures consisting of three layers: poly-L-lactide (PLLA), 8% Eudragit E 100 + Eudragit RS 100, and Chitosan. The amount of fluoride ion (F) released was determined with an ionmeter. In order to assess the effect of this antimicrobial material releasing NaF in a controlled manner on S. mutans, the proliferation of this organism was recorded by preparing test discs with a standard surface area containing the active ingredient. In all the groups the F release began when the pH fell under 5.5, after 6 hr, and the number of S. mutans declined. In conclusion, the newly developed controlled release system can release intraorally the fluoride ion with its anti-caries properties when the pH falls below 5.5 and it may help significantly to improve caries prevention.