INTRODUCTION: The fluoride varnish and fluoride-releasing composites are being used in orthodontic patients to prevent white spot lesions (WSL). The study evaluates and compares the efficacy of these two on plaque accumulation, gingival health, and demineralization in vivo, as well as shear bond strength in vitro. METHODS: This study was conducted using 45 extracted premolars for the in vitro group and 45 patients for the in vivo group. Each group was further subdivided into three subgroups of 15 each. In the in vitro subgroups, bonding in Subgroup I (control group) was done using Transbond XT, Subgroup II (fluoride varnish group) involved the application of fluoride varnish using Fluor Protector, and Subgroup III (Transbond Plus Color Change Adhesive) was used for bonding. Shear bond strength was evaluated in the in vitro group using a universal testing machine. In the three in vivo subgroups, bonding was done similarly to the in vitro group. The efficacy was assessed in vivo using the plaque index (PI), gingival index (GI), and demineralization index at T0 (baseline), T1 (week 4), T2 (week 8), and T3 (week 12). RESULTS: The results demonstrated a statistically significant difference between the inter- and intragroup comparisons of the PI and GI, whereas the demineralization index group did not show any statistically significant difference, as indicated by ANOVA, Tukey's test, and paired t-tests. The in vitro group showed statistically significant differences between the fluoride varnish group and both the control group and the fluoridated composite group. CONCLUSION: Fluoride-releasing orthodontic composite and fluoridated varnish can be used to prevent plaque accumulation and demineralization and maintain gingival health during fixed orthodontic therapy.