Recurrent aphthous stomatitis (RAS) is a common, painful, and ulcerative disorder of the oral cavity with unknown etiology. Treatment is a highly controversial topic. The aim of this study was to evaluate the clinical efficacy of a novel paste containing Myrtus communis (Myrtle) in the treatment of recurrent aphthous stomatitis. Myrtle is a particular herb used in some cultures as treatment for mouth ulcers. The study was a randomized, double-blind, controlled before-after clinical trial. Forty-five patients with RAS randomly participated in this study. The subjects were treated with placebo paste and myrtle oral paste in two consecutive episodes. The paste was applied by subjects themselves four times a day for 6 days. Five parameters (size change, pain scale, erythema and exudation level, oral health impact profile, and patient overall assessment of their treatment) were recorded both before (baseline) and during each episodes of treatment (on the morning of days 2, 4, and 6). There were no statistically significant differences between baseline parameters (p > 0.05). The data indicated a statistically significant reduction of ulcer size (p < 0.001), pain severity (p < 0.05), and erythema and exudation level (p < 0.001). Oral Health Impact Profile improved significantly in the treatment group (p < 0.001). Patient overall assessment of their treatment improved after applying paste containing myrtle (p < 0.05). No side effects were reported. This study has shown myrtle to be effective in decreasing the size of ulcers, pain severity and the level of erythema and exudation, and improving the quality of life in patients who suffer from RAS.