Background: The cost-effectiveness of this study was achieved in the group that was treated every three months with periodic intervals, which had a reduction of caries with 62%. The relative effectiveness of our study is the application of fluoride treatment every 3 months compared with treatments done every 4 and 6 months, respectively. Objective: To evaluate the reduction of caries disease depending on the time period of fluoride gel application. The sample was chosen randomly. Main hypothesis: The frequency of fluoride gel application every 3 months has positive impacts on reducing dental caries. Basic design: This is a cross-sectional study with a controlled sample for a period of 24 months. Durashield fluoride fluid (5% sodium fluoride) was used for the treatment of permanent dentition of the 6–10-year-old children. Clinical setting: This study proves that fuoride application every 3 months significantly reduces caries morbidity. Participants: Our study included 400 children, who were divided into 4 groups, 100 children in each group. Intervention: The first group did not undergo any treatment and it is called the control group. The second group was under fluoride treatment every 4 months. The third group was treated with fluoride every 3 months, and the fourth group was treated every 6 months. Results: The data collected from the control group showed that there is an increase in 24% of the caries incidence. In the group treated with fluoride every 4 months, caries incidence decreased to 30%. The group treated every 3 months with periodic intervals had a reduction of caries with 62%, while the group treated every 6 months had a reduction of 40%. Based on the analysis of variance (ANOVA) test, the fluoridation application every 3 months is significant for p = 0.000. Conclusion: The best results were achieved in the treatment with fluoride in a 3-month periodic interval.