Purpose: This study was carried out to evaluate the effectiveness of different fluoride applications on periodontal health (clinical and microbiological) during orthodontic treatment with fixed appliance. Patients & Methods: The study groups were designed randomly into three equal groups using the same type of (fluoride-free) toothpaste. Group I used PERIOMED contains stannous fluoride mouthwash, group II used LISTERINE® contains sodium fluoride Mouthwash and the control group used distilled water. All patients were put onto the recall schedule at zero, 7th, 14 and 28 days. Samples were collected for detection of the interleukin-1 beta level, determination of reduction in microbial count and assessment of the following clinical parameters: pocket depth, plaque index, and gingival index. They were recorded at these time intervals mentioned. Following Orthodontic treatment for all patients, Interleukin- 1 beta and Colony Forming Units (CFUs) were measured. Results: interleukin-1beta level and bacterial count were high at the onset of periodontal inflammation at the same range with no significant differences between the studied groups. At the end of the study, group I and group II showed a marked decrease in the interleukin-1beta level and bacterial count compared to the control group, and there was a statistically nonsignificant difference between group I & II. Conclusion: Stannous fluoride mouthwash showed the best results in the level of IL-1β, since in the reduction of the bacterial count also includes improving in the clinical parameters (PD, PI, GI) compared with the other samples of the study.