Objectives Oral lichen planus (OLP) is a chronic disease with immune-mediated pathogenesis. Selenium (Se), an antioxidant, plays a role in modulating immunity. The aim of this clinical trial was to evaluate 2 Se forms (novel topical hydrogel and oral capsules), solely, in treating erosive OLP based on clinical evaluation and salivary oxidative stress markers. To date, to our knowledge, this is the first study to evaluate the role of Se solely in treating erosive lesions associated with erosive OLP. This clinical trial has been registered in the Cochrane Database under registry number PACTR201901531815403. Methods Patients were allocated into 1 of 3 groups: group I, topical corticosteroids and topical antifungal as an adjunctive therapy; group II, novel topical Se hydrogel; or group III, systemic Se. Treatment lasted for 6 weeks. Patients were clinically evaluated at baseline and at 6 and 12 weeks for reduction in pain scores and clinical lesion size. Biochemical analysis was performed for salivary malondialdehyde (MDA) and total antioxidant capacity (TAC) levels at baseline and 6 weeks. Correlation between clinical signs and symptoms and salivary oxidative stress markers was measured at 6 weeks. Two-way analysis of variance (ANOVA) followed by a post hoc Tukey test was performed to assess for significant differences in mean pain scores, clinical lesion size, and salivary MDA and TAC levels at 6 weeks. One-way ANOVA was used to test for significant variations in clinical parameters at 12-week follow-up. Principal component analysis and nonmetric dimensional scaling were performed to test for correlation and possible relationships between clinical parameters and salivary oxidative stress markers. Results There was a significant reduction in signs and symptoms in response to all treatment modalities. However, there was no significant difference among the 3 groups at 6 weeks. At 12 weeks, group II had significantly lower pain scores than group I. Salivary MDA levels showed a significant decrease in patients in group I and group III. TAC levels showed no significant difference in response to treatment. Conclusions Se can be proposed as a treatment for OLP. Salivary MDA levels can be a biomarker for OLP disease severity. Oral lichen planus (OLP) is a chronic disease with immune-mediated pathogenesis. Selenium (Se), an antioxidant, plays a role in modulating immunity. The aim of this clinical trial was to evaluate 2 Se forms (novel topical hydrogel and oral capsules), solely, in treating erosive OLP based on clinical evaluation and salivary oxidative stress markers. To date, to our knowledge, this is the first study to evaluate the role of Se solely in treating erosive lesions associated with erosive OLP. This clinical trial has been registered in the Cochrane Database under registry number PACTR201901531815403. Patients were allocated into 1 of 3 groups: group I, topical corticosteroids and topical antifungal as an adjunctive therapy; group II, novel topical Se hydrogel; or group III, systemic Se. Treatment lasted for 6 weeks. Patients were clinically evaluated at baseline and at 6 and 12 weeks for reduction in pain scores and clinical lesion size. Biochemical analysis was performed for salivary malondialdehyde (MDA) and total antioxidant capacity (TAC) levels at baseline and 6 weeks. Correlation between clinical signs and symptoms and salivary oxidative stress markers was measured at 6 weeks. Two-way analysis of variance (ANOVA) followed by a post hoc Tukey test was performed to assess for significant differences in mean pain scores, clinical lesion size, and salivary MDA and TAC levels at 6 weeks. One-way ANOVA was used to test for significant variations in clinical parameters at 12-week follow-up. Principal component analysis and nonmetric dimensional scaling were performed to test for correlation and possible relationships between clinical parameters and salivary oxidative stress markers. There was a significant reduction in signs and symptoms in response to all treatment modalities. However, there was no significant difference among the 3 groups at 6 weeks. At 12 weeks, group II had significantly lower pain scores than group I. Salivary MDA levels showed a significant decrease in patients in group I and group III. TAC levels showed no significant difference in response to treatment. Se can be proposed as a treatment for OLP. Salivary MDA levels can be a biomarker for OLP disease severity.