Periodontal tissue inflammatory diseases constitute one of the most common oral pathologies. Treatment protocols include professional oral hygiene and the use of antiseptic solutions. Currently, the use of chlorhexidine bigluconate solution is widespread. However, a sufficient number of studies have recently shown the formation of resistance in periodontopathogenic bacteria to chlorhexidine, which indicates a decrease in the effectiveness of chlorhexidine in the treatment of periodontal diseases. Polyhexanide solution is used as a modern antiseptic in surgery, which demonstrates effective antimicrobial action and the ability to destroy biofilms formed by bacterial colonies. To conduct a comparative analysis of the antiseptic solution cytotoxicity on human gingival cells to evaluate the safety of using polyhexanide solution in treatment protocols for inflammatory periodontal disease. Materials and methods Primary culture of human gingival mesenchymal stromal cells was used for the study. Cell counting and viability determination were performed automatically using Countess II cell counter, in disposable slides. Using the flow cytofluorimetry method with staining with fluorescent dyes Annrxin/Propidium Iodide, the viability of gingival cells in early passages was analyzed. The results of this study showed that activation of apoptosis and necrosis processes was observed during exposure to antiseptic solutions. Inflammatory diseases of periodontal tissues currently occur worldwide with a fairly high frequency. The development of new treatment protocols may contribute to improving the effectiveness of periodontal disease treatment. Polyhexanide solution may be promising for inclusion in therapy protocols and can be safely used instead of chlorhexidine. © 2025 Elsevier B.V., All rights reserved.