Purpose: Vaginal lubricants are widely used by women to resolve intercourse difficulties or as performance enhancers. However, little information is available regarding the safety of over-the-counter (OTC) lubricants. Therefore, in this study, a set of commercial lubricant products available on the Korean online market were selected and evaluated in vitro for their safety relevant to their osmolality. Materials and Methods: Five commercially available gel-based OTC lubricant products were included in this study. Osmolality was determined using a vapor pressure 5520 osmometer. Cell viability was measured by MTT assay and Western blotting. Human vaginal tissue integrity was measured by immunohistochemistry. Results: Four OTC lubricant showed hyper-osmolality, while one OTC lubricant was within the minimum WHO-recommended standards. The findings showed that four hyperosmolal OTC vaginal lubricants showed cellular damage to the cultured vaginal cell line and human vaginal explant. One iso-osmolal OTC vaginal lubricant showed less cellular damage to both cultured vaginal cell lines and human vaginal explants. Conclusion: Present study showed that the osmolality of OTC vaginal lubricant is a major factor affecting epithelial cell survival and tissue integrity. The effect of each ingredient contained in OTC lubricants was not considered. Thus, additional research is needed to evaluate formulae to enable production of safer OTC vaginal lubricants.