Purpose: The purpose of this study was to evaluate the effects of the antimicrobial photodynamic therapy (aPDT) with red light and different mouth rinses with photosensitizers (PS) on oral disinfection within 30 minutes of the application. aPDT is a procedure associating a drug (PS) and a light source, resulting in a contamination reduction. Recently, aPDT has been investigated for oral decontamination. This study suggests the possibility of using aPDT as a very simple method for bacterial reduction in the oral environment in the occasion of procedures. Methods: A randomized clinical trial was performed with eighty patients divided into 8 groups: G1-methylene blue 0.05%+LED; G2-hydrogen peroxide 3%+methylene blue 0.05%+LED; G3-Photogem 0.05%+LED; G4-hydrogen peroxide 3%+Photogem 0.05%+LED; G5-Photodithazine 0.05%+LED; G6-Photodithazine 0.05%; G7-chlorhexidine 0.12%+LED; G8-chlorhexidine 0.12% (control group). Irradiation parameters were: 640 ± 5 nm; 180 mW/cm²; 60 J/cm². Saliva samples were collected at baseline and after the experimental phase (0 and 30 minutes). Samples were cultured on blood agar plates under microaerophilic conditions. Results: G2 and G4 resulted in better bacterial reduction than their counterpart groups (G1 and G3, respectively). G4 and G6 provided the best results, with G6 being able to sustain the bacterial reduction for at least 30 minutes. Conclusions: Based on our results, aPDT seems to be a reliable approach for oral decontamination, with Photodithazine being the best PS. Such result allows next steps towards the use of pre-procedure decontamination using photodynamic action.