Background: Orthodontic patients are often instructed to use fluoride mouthrinses (FMR) to prevent caries during treatment with fixed orthodontic appliances (FOA). The aim of this study was to examine the caries preventive effect of FMR during FOA treatment based on randomized controlled trials. Methods: An information specialist searched five databases up to September 30, 2024. We included trials with parallel groups (intervention vs. control) and a minimum duration of six months. Based on the abstracts, the authors independently selected and reviewed full text papers, extracted key outcome data, and assessed the risk of bias. The primary outcome was incidence of enamel caries on subject level. We conducted a narrative synthesis and pooled comparable data in a random effects model. Results: We identified 22 studies of which seven, involving 704 patients, met the inclusion criteria. Five and two studies had moderate and high risk of bias, respectively. In all studies, FMR was additive to daily use of fluoride toothpaste. The intervention varied from twice daily to twice weekly and the duration ranged from six to 26 months. Five studies were included in a meta-analysis. The aggregated data showed a small risk difference of − 0.07 (95% CI -0.14; -0.01) in initial caries development adjacent to bracket base between the experimental and the control groups. Conclusion: This review found insufficient support for a general recommendation to use FMR during treatment with fixed orthodontic appliances in populations with regular use of fluoride toothpaste. This does not rule out the possibility that individual orthodontic patients may benefit from FMR after comprehensive risk assessment. Further investigations with standardized interventions and duration, reporting a core outcome set are required to clarify the effectiveness of fluoride mouthrinses in orthodontic patients.