Aim: This study was carried out to evaluate the antibacterial activity of a mouthwash containing clusters of zinc-carbonate hydroxyapatite nanoparticles in combination with chlohexidine or fluoride.Materials and methods: Antimicrobial agents used in this study were Chlorhexidine diacetate, Sodium fluoride powder and Dr.Wolff’s Biorepair against Streptococcus mutans (MS). In this study, the relative antimicrobial efficacy of newly introduced zinc-carbonate hydroxyapatite nanoparticels containing mouthwash, chlorhexidine, sodium fluoride and their combination against MS was tested. The MS was inoculated onto its specified culturel media. Agar diffusion test is done. The inhibition zone diameters were measured. Mean inhibition zone diameters were recorded and statistically analyzedResult: For the effect of the tested antibacterial on the Streptococcus mutans, results showed that the mean diameter and standard deviation of inhibition zone (mm) for chlorhexidine (CHX) was 23.9 (2.04) mm, sodium fluoride (NaF) was 12.2 (0.75) mm, hydroxyapatite microclusters containing mouthwash (HAPMC) was 18.2 (1.3) mm, HAPMC+CHX was 22.5 (2.6) mm and HAPMC+NaF was 18.7 (1.8) mm.Conclusion: Hydroxyapatite microclusters containing mouthwash had a potential antimicrobial activity against MS alone or in combination with other antimicrobials.