Aim <p>This study aims to examine the mediating role of psychological resilience in the relationship between perceived stress and spiritual well-being among women. By focusing on a large sample of Turkish women, it provides one of the first quantitative insights into how cultural and spiritual traditions shape gender-specific coping mechanisms, thereby offering a novel contribution to the international literature on stress and spirituality.</p> Materials and methods <p>A cross-sectional survey was conducted with 498 women residing in Istanbul. Participants completed the Brief Resilience Scale, the Spiritual Well-Being Scale, and the Perceived Stress Scale–Short Form. Data were analyzed using confirmatory factor analysis for construct validity, correlation analysis, and path analysis with the bootstrap method (5.000 iterations) to test the mediation hypothesis.</p> Results <p>Women reported moderate stress (M = 2.97) and resilience (M = 3.20), but high spiritual well-being (M = 3.81). Stress negatively correlated with resilience (<i>r</i> = − .457, <i>p</i> = .000) and spiritual well-being (<i>r</i> = − .117, <i>p</i> = .009). Resilience showed a weak positive correlation with spiritual well-being (<i>r</i> = .109, <i>p</i> = .015). Path analysis indicated a significant direct association of stress on spiritual well-being (β = -0.123, <i>p</i> = .006), but the indirect association through resilience was not significant (β = -0.005, <i>p</i> = .530). In other words, psychological resilience does not have a mediating role in the association of perceived stress on spiritual well-being.</p> Conclusion <p>Our findings indicate a small but significant negative association between perceived stress and spiritual well-being, suggesting that higher stress levels were related to lower spiritual well-being. These findings underscore the need for culturally sensitive health interventions that integrate spiritual coping strategies alongside resilience-building approaches.</p>