Aim: To assess the efficacy of Sage extract or Chlorohexidine-based mouthwashes on the detected percentage of recovery of Streptococcus mutans and its pathogenicity by real-time polymerase chain reaction (PCR) in high caries risk patients over one-month follow-up. Methodology: A total number of 74 high caries-risk patients were assigned to this study. Participants were randomly divided into two groups (n=37) according to the type of mouthwash (A) where group (A1) patients used Sage extract containing mouthwash while group (A2) participants used chlorohexidine-containing mouthwash. The traditional microbiological cultivation method of S.mutans and quantitative real-time polymerase chain reaction was employed to analyze the bacterial count of each salivary sample at baseline (T0), after two weeks (T1) and after four weeks (T2) of using mouthwashes. Results: Comparison of antimicrobial effectiveness across CHX and sage groups revealed a significant difference concerning oral streptococcus count. Sage extract as a natural product had a significantly higher value than CHX (p<0.001) in decreasing log bacterial count. Comparing bacterial cultural method and real-time PCR, real-time PCR was more specific and sensitive in detecting S.mutans.