This study aimed to investigate the possible moderating role of sexual sanctification in the context of sexual dysfunctions and sexual and psychological well-being, particularly examining potential gender differences. Data were collected from 1207 Israeli adult women and men in cohabiting relationships for at least 6 months using an online survey. Participants provided information on sexual functioning, and measures included non-theistic sexual sanctification, sexual and psychological distress, and sexual and relationship satisfaction. Measures of religious behavior and belief were also included as control variables. Statistical analyses included moderation models to assess the moderating function of sexual sanctification on the associations between sexual dysfunctions and the outcome measures. Separate analyses were performed for men and women. Findings confirmed significant associations between sexual dysfunctions and all aspects of sexual and psychological well-being included in the study for women and men. Sexual sanctification was found to moderate the association between sexual dysfunctions and sexual and psychological distress, particularly for men, where at higher levels of sanctification, the association between dysfunction and distress was more pronounced. However, sexual sanctification did not significantly moderate the relationships between sexual dysfunctions and sexual or relationship satisfaction for either gender. The results suggest that, although sexual sanctification is often associated with positive outcomes, it may also exacerbate the emotional impact of sexual dysfunctions, particularly in those who perceive their sexual experiences as sacred. Gender-specific patterns further emphasize the importance of tailored interventions that consider the different ways men and women experience and interpret sexual dysfunctions within the context of their sexual perceptions.