Objectives: This study was conducted to evaluate the antimicrobial effect of mouthwashes containing nanohydroxyapatite (Nno-HAp) and povidone-iodine (PVP-I) in comparison with chlorhexidine (CHX) on Streptococcus mutans in saliva. Subjects and Methods: Thirty children having high caries index aged between 6-12 years were included in the study following specific inclusion criteria and then grouped randomly into three main groups based on the used mouthwash (Chlorohexidine; Povidoneiodine; Nanohydroxyapatite). Two Saliva samples were collected pre-& post 15 days mouthwash rinsing from each child. Another saliva sample was taken after 15 days of mouthwash discontinuity. The samples were transported immediately to the bacterial lab for culturing and counting. The efficacy of mouthwashes were assessed. Results: After 15 days of mouth-rinsing, all tested mouthwashes revealed a significant reduction in Streptococcus mutans count. CHX mouthwash showed the highest antibacterial effect followed by PVP-I and Nano-Hap with a high significant difference between them. However, after 15 days of discontinuity, it was found that there was a significant difference between chlorohexidine and Nano-hydroxyapatite groups only. Conclusion: Although Mouthwashes containing PVP-I and Nano-HAp showed a high antimicrobial effect against streptococcus mutans, however, CHX mouthwash is still the most effective against Streptococcus mutans.