Introduction. The microbiota of the oral cavity and oropharynx, actively interacts with the epithelium of the mucous membrane and the immune system, creates antagonistic conditions for the growth and reproduction of pathogens. Microbiocenosis-preserving therapy can provide conditions for maintaining colonization resistance and reduce the likelihood of adhesion of respiratory viruses.Aim. To evaluate the effect of local use of various antimicrobial drugs on the microbiota of the oropharyngeal mucosa in children with acute respiratory infection.Materials and methods. 120 children (5–10 years old) with acute respiratory infection were divided into three groups, in which they were used as part of complex therapy: in group 1st – hexetidine-containing aerosol, in group 2nd – a children’s spray containing gramicidin S and cetylpyridinium chloride, in the 3rd – 0.01% solution of benzyldimethyl-myristoylamino-propylammonium. On the 1st and 12th days of observation, participants had a throat swab taken to study the state of the oropharyngeal microbiota using 16S rRNA sequencing. The results obtained were compared with those of healthy peers.Results. According to sequencing data, the microbiota of participants in all groups before treatment differed from the microbiota of healthy peers in terms of alpha and beta diversity, as well as in the results obtained by the nearest balance method. Local use of antiseptic drugs influenced the microbiota at the level of species and genera of microorganisms. After treatment in the 2nd group, in contrast to the 1st and 3rd, statistically significant changes in the balances at the level of microorganism species were revealed towards the indicators of healthy peers.Conclusions. A combined drug containing cetylpyritinium chloride and the bacteriocin-like antimicrobial peptide gramicidin S demonstrated no negative effect on commensal microbiota and contributed to the stabilization of the regional microbiota.