Background: Treatment with fixed orthodontic appliances has been associated with significant biofilm accumulation, thus putting patients at a higher risk of oral health deterioration. The use of probiotics has been proposed to be useful in the prevention or treatment of oral pathologies such as caries and diseases of periodontal tissues. Our aim was to investigate the effects of probiotic use on inflammation of the gingival tissues and the decalcification of the enamel in patients being treated with fixed orthodontic appliances. Methods: We searched without restrictions 8 databases and performed hand searching until September 2019. We searched for randomized controlled trials (RCTs) evaluating whether individuals with fixed orthodontic appliances benefit from probiotic treatment in terms of the inflammation of the gingivae and decalcification of the enamel. Following the selection of studies and the extraction of pertinent data, we appraised the risk of bias and the confidence in the observed effects based on established methodologies. Results: From the final qualifying studies, three did not show any statistically significant effect on gingival inflammation after probiotic administration of up to 1 month. Similarly, non-significant differences were noted in another study regarding white spot lesions development (mean administration for 17 months). No adverse effects were reported and the level of evidence was considered moderate. Conclusions: Supplementation of orthodontic patients with probiotics did not affect the development of inflammation in the gingivae and decalcification in the enamel. Additional RCTs, with longer intervention and follow-up periods, and involving different combinations of probiotic strains are required. Trial registration: PROSPERO (CRD42018118008)