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Background: This systematic review and network meta-analysis aimed to assess comparative efficacy and safety of interventions to treat symptomatic, biopsy-proven oral lichen planus (OLP). Methods: Search was conducted for trials published in Medline, Embase and Cochrane Central Register of Controlled Trials. Network meta-analysis was performed on data from randomized controlled trials that assessed efficacy and safety of interventions used in the treatment of OLP. Agents were ranked according to their effectiveness in treatment of OLP based on outcomes using surface under the cumulative ranking [SUCRA]. Results: In total, 37 articles were included in the quantitative analysis. Purslane was clinically significant and ranked first in improving clinical symptoms [RR = 4.53; 95% CI: 1.45, 14.11], followed by aloe vera [RR = 1.53; 95% CI: 1.05, 2.24], topical calcineurin [RR = 1.38; 95% CI: 1.06, 1.81] and topical corticosteroid [RR = 1.35 95% CI: 1.05, 1.73]. Topical calcineurin demonstrated the highest incidence of adverse effects [RR, 3.25 [95% CI: 1.19, 8.86. Topical corticosteroids were significant in achieving clinical improvement of OLP with RR1.37 [95% CI: 1.03, 1.81]. PDT [MD = −5.91 [95% CI: −8.15, –3.68] and showed statistically significant improvement in the clinical score for OLP. Conclusions: Purslane, aloe vera and photodynamic therapy appear promising in treatment of OLP. More high-quality trials are recommended for strengthening the evidence. Although topical calcineurin is significantly efficacious in the treatment of OLP, significant adverse effects are a concern for clinical use. Based on the current evidence, topical corticosteroids are recommended for treatment of OLP owing to their predictable safety and efficacy.

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