Background <p>Frailty is a significant factor affecting the quality of life of stroke patients. psychological distress is an essential factor affecting depression in stroke patients. However, the mediating role of depression between psychological distress and debilitation has not been explored.</p> Methods <p>In this study, 315 stroke patients in Shandong and Liaoning provinces were investigated by convenience sampling method from May 2024 to October 2024. Questionnaires included Frailty Scale and Psychological Distress and Depression scale.</p> Results <p>In this study, psychological distress scores (4.16 ± 2.29), depression scores (8.81 ± 4.55) and frailty scores (8.92 ± 4.09) were obtained. There was a significant positive correlation between depression and psychological distress in stroke patients (<i>r</i> = 0.483, <i>P</i> &lt; 0.001), depression and frailty (<i>r</i> = 0.575, <i>P</i> &lt; 0.001). There was a significant positive correlation between psychological distress and frailty in stroke patients (<i>r</i> = 0.391, <i>P</i> &lt; 0.001). The direct effect of psychological distress in stroke patients was 0.264. The direct mediating effect of depression on psychological distress and frailty was 0.435.</p> Conclusion <p>This study provides further insights into the psychological mechanism of psychological distress and frailty in stroke patients. Clinicians and nurses can actively help stroke patients reduce psychological distress, reduce the depression of stroke patients, so as to reduce the occurrence of frailty and improve the quality of life of patients.</p>