Recurrent aphthous stomatitis is the most common oral mucous ulcerative lesion with challenging treatment. Herbal medicine therapy can propose clinical efficacy and safety due to its large biological activities. The objective was to review the clinical efficacy and safety of herbal medicine therapy in terms of ulcer size, pain score, healing duration, and adverse effects in recurrent aphthous stomatitis. A systematic was conducted based on the PRISMA statement. The search was performed using four electronic databases, namely PubMed, Cochrane, Science Direct, and Google Scholar for articles published from 2016 until 2021 using specific keywords. The search was limited to randomized controlled trials (RCTs), in English, full text, and study in humans. The main outcome is expected to be ulcer size, pain score, healing duration, and adverse effects. Quality assessment of selected articles was conducted using the Quality Appraisal of Randomized Trials Checklist (Cochrane Risk of Bias tool). The methodology quality of studies was evaluated using the Cochrane Handbook for Systematic Review of Interventions and Rev Man software. Five articles were eligible for analysis. The population of the sample study ranged from 34-70 patients of 15-65 y old. The herbs used were Aloe vera (Aloe barbadensis Miller), curcumin (Curcuma longa), licorice (Glycyrrhiza glabra), tobacco (Nicotiana tabacum L.), and pomegranate (Punica granatum Linn.). This review showed that there is some evidence of the clinical efficacy and safety of herbal medicine therapy in improved outcomes of recurrent aphthous stomatitis treatment with minimum adverse effects.