To investigate the effect of a probiotic supplement on the severity of aphthous lesions in patients with recurrent aphthous stomatitis (RAS) over a 3-month period. A second endpoint was to study the effect on pain related to the lesions. The study employed a double-blind randomized, placebo-controlled design with two parallel arms. Twenty patients with minor and major RAS were consecutively enrolled and randomly assigned to the test or the control group. The intervention consisted of lozenges containing two strains of Lactobacillus reuteri taken twice daily for 90 days. Ulcer Severity Score (USS) consisting of six lesion characteristics (number, size, duration, ulcer-free period, site, and pain) was calculated at baseline and after the intervention. Oral pain related to the lesions was estimated by the patients with a Visual Analogue Pain Scale. An improvement of the USS, as well as oral pain, was evident in both groups after 90 days but the reduction was only statistically significant (p < 0.05) compared with baseline in the test group. There were no significant differences between the groups, neither at baseline nor at follow-up. No side effects were recorded. Daily supplements with L. reuteri reduced the severity of aphthous lesions over a 90-day period but the improvement was not significantly better than placebo. The results encourage further research and provide a basis for power calculations of larger and extended studies. ClinicalTrials.gov Identifier: NCT02976922.