The aim of this study was to evaluate the effect of drops containing probiotic bacteria on the recurrence of dental caries in preschool children. The study employed a randomized, placebo-controlled, double-blinded design with two parallel arms. 38 preschool children were enrolled after comprehensive restorative treatment under general anesthesia or conscious sedation (baseline), and they were followed up after 6 and 12 months. Parents of children in the test group were instructed to give 5 daily drops containing two strains of Limosilactobacillus reuteri (DSM 17938 and ATCC PTA 5289) at bedtime. The placebo drops were identically composed but lacked bacteria. The duration of the intervention was 12 months. The primary endpoint was recurrence of new caries lesions on subject level (yes/no), and secondary endpoints were presence of dental plaque and gingivitis. We found high rate of recurrent moderate and extensive lesions after 12 months (67%) but there were no significant differences between the groups. We observed no beneficial effects on dental plaque or gingival inflammation. The findings were however uncertain and inconclusive due to lack of power, a consequence of the COVID-19 pandemic. ClinTrials.gov Identifier: (NCT04929340), June 18, 2021; retrospectively registered.