Introduction: The vagina is a finely balanced microecological environment. The rupture of this balance leads to dysbiosis, which causes the resident microbiota to be overcome by pathogens. This event triggers the onset of gynecological infectious diseases, normally treated with antimicrobial drugs, considered to date as the gold standard; yet the increasing rate of drug resistance requires novel approaches and alternative therapeutic strategies. Bacterial lysates, obtained by mechanical or chemical crushing of the bacterial cell walls, contain several antigens and Pathogen-Associated-Molecular-Patterns (PAMP) molecules that through the priming of epithelial and innate immune cells could improve the responses to the pathogens. Materials and methods: We evaluated the effect of a bacterial lysate (BL) obtained by Results: BL did not show any direct antimicrobial effect nor any toxicity for the cell lines employed. Upon infection with Discussion: Overall, the results shown here point to the possible role of BL in priming epithelial and phagocytic cells and to improve their response against bacterial and fungal pathogens. These data indicate that the use of this (and, in future, other bacterial lysates) may provide a promising novel approach to handle lower genital tract infections through the reinforcement of local immunity.