Introduction. The mucous membrane of the oral cavity is part of a single system of mucosal immunity and implements functions at the level of local and systemic immunity. Microflora together with innate immunity receptors (TLR, NLR, etc.) regulates the colonization resistance of mucous membranes, determines the severity of the infectious process and maintains the normocenosis of the oral cavity. Violations of the dynamic balance of colonization resistance can lead not only to dental caries, but also to other pathologies of both the oral cavity and the whole organism. The aim of this study was to estimate the levels of α-defensins and secretory immunoglobulin A (sIgA), as well as representatives of the microbial community of the oral cavity of young people aged 19-22 years with caries of the occlusal and contact surfaces of posterior teeth against the background of prophylactic use of Licopid® 1 mg (glucosaminyl muramyl dipeptide, GMDP). Material and methods. In 43 clinically healthy patients 19-22 years old with caries of the occlusal and contact surfaces of the lateral teeth, oral fluid was taken before taking the drug and 14 days after. Patients of the main group of 21 people from 1 to 10 days of observation received drug Licopid® (1 mg) (GMDP, AO Peptek, Moscow, Russia) sublingually, 1 tablet once a day. Participants of the comparison group (22 patients) did not received Licopid®. Oral fluid microbiota was assessed by RT-PCR using Dentoflor reagents («DNA-technology», Moscow). Primers V6 16S rDNA were used for NGS DNA sequencing on an MiSeq instrument (Illumina, USA). Microorganisms were identified using the Blast software. The analysis of α-defensins HNP1-3 and the content of sIgA in sublingual saliva were studied by enzyme-linked immunosorbent assay using Hycult Biotech (USA) and Vector-Best (Novosibirsk, Russia) reagents. For statistical processing of the data the Mann-Whitney test was used and the Biostat software. Results. The use of the drug Licopid® 1 mg helps to restore the levels of α-defensins HNP1-3 and sIgA to the level of those in individuals with intact teeth, leads to a significant decrease in the representation of Porphyromonas gingivalis and Clostridium difficile and increases the diversity of oral microflora. Conclusion. The use of Licopid® 1 mg after the caries treatment is accompanied by the correction of immunological parameters in the oral fluid. © 2021 Meditsina Publishers. All rights reserved.