Objective(s): Chlorhexidine 0.2% mouthwash is commonly used in orthodontic patients for plaque control. But it has some side effects. Metal oxide nanoparticles have been recently used in mouthwashes in reports. So we aimed to evaluate antibacterial effect of ZnO and Ag/ZnO nanoparticles against Streptococcus mutans and compare them with chlorhexidine 0.2%, sodium fluoride 0.05% and some of their compositions. Materials and Methods: ZnO and Ag/ZnO NPs were synthesized and sixteen groups of mouthwashes were prepared. We used Zone of Inhibition (ZOI) test to evaluation of antibacterial effects of as-prepared mouthwashes, against S. mutans. The cytotoxicity of the ZnO and Ag/ZnO NPs were investigated in the A549 cell line.Results: Among the study groups, the maximum ZOI (16.60±0.49 mm) pertained to Ag/ZnO, 10 mg NPs plus 100 ml base material, (Ag/ZnO b 10). The results indicate that no significant harmful effect is imposed to the cells up to 0.2 mg/ml of ZnO and Ag/ZnO NPs.Conclusion: Results showed that mouthwash containing Ag/ZnO b 10 has the highest antibacterial properties against S .mutans amoung study groups and because in this concentration it is safe for cells, so it can be served as an alternative mouthwash in plaque control instead of chlorhexidine 0.2% after in vivo studies.