Background. Lichenoid reactions of the oral mucosa are currently recognized as a serious issue for dentists of various specialties, since their knowledge and competence in the diagnosis and pathogenetic treatment of lichenoid lesions of the oral cavity are yet to be improved. Following the data on high oncogenic potential in some forms of lichenoid reactions of oral cavity mucous membranes, the issue should be given serious considerations, and dentists should keep oncology-related suspicion when receiving these patients.Objective. To evaluate the efficacy of comprehensive dental treatment for lichenoid reactions of the mucoparodontal complex.Methods. A single-center pilot cohort study was conducted to evaluate the efficacy of the comprehensive treatment (combination of pharmacotherapy and physiotherapy) of patients with lichenoid reactions of the oral mucosa. The observation group consisted of 49 patients (15 males, 34 females) aged 58.92 ± 0.82 years with verified diagnoses of oral mucosa lichenoid reactions. The suggested treatment included pharmacotherapy (highly-potent topical steroids, calcineurin inhibitors) and physiotherapy in the form of low level laser therapy (635 nm, 10 W) provided via Matrix laser (Matrix, Russia). Treatment efficacy was assessed by the total scale of treatment efficacy, registering indicators of the area of focal lesions and the severity of pain syndrome, as well as by changes in dental quality of life indicators according to OHIP-49-RU (Oral Health Impact Profile) in the Russian version. Statistical processing of the data involved Student’s t-test and Wilcoxon t-test. Differences were considered significant at p ≤ 0.05. Data statistical analysis was performed using SPSS 13.0 (SPSS Inc., USA).Results. During the follow-up period, the indicators of the total scale of treatment efficacy decreased significantly (p < 0.001) in 100% of patients and amounted (as medians and quartiles): 6.0 (4.0–7.0) points before treatment and 1.0 (1.0–2.0) points after treatment to be objectified by a significant reduction in the area of focal lesions (by 63.2%, p < 0.001) and in pain syndrome (spontaneous pain from 2.0 (1.5–3.0) points before treatment to 0.0 (0.0–1.0) points after treatment; induced pain from 3.0 (2.0–3.0) points to 1.0 (0.0–1.0) points). Along with the clinical improvement, the scores in dental quality of life improved from 83.11 ± 2.58 to 39.94 ± 0.86 points, according to OHIP-49 RU (Oral Health Impact Profile).Conclusion. Early detection and differentiation of lichenoid reactions in oral mucous membranes ensure timely treatment using the developed protocol of comprehensive treatment (combination of pharmacotherapy and physiotherapy). The efficacy of the protocol was confirmed clinically and justified in relation to quality of life.