Purpose: Rectal prolapse is still a relatively understudied medical condition, especially in women, whereas physical symptoms, depressive symptoms, and quality of life (QOL) in women with pelvic organ prolapse have been steadily studied. This study aimed to examine the interaction and main effects of physical and depressive symptoms on physical and mental QOL of women seeking care for rectal prolapse in Korea. Methods: Ninety-two women with rectal prolapse were recruited from a colorectal surgery clinic of a tertiary teaching hospital in Gwangju, Korea. Physical symptoms related to rectal prolapse (pelvic organ prolapse distress, POPD; colorectal-anal distress, CRAD; and urinary distress, UD), depression, and QOL were measured. The data were analyzed using descriptive statistics, Pearson correlation coefficient, and two-way analysis of variance. Results: The interaction between POPD symptoms and depressive symptoms (F=4.51, p=.037) affected physical QOL. The interaction between POPD (F=9.66, p=0.003) and CRAD symptoms (F=7.48, p=.008), respectively, and depressive symptoms affected mental QOL. Depressive symptoms had a significant main effect on the physical QOL in the CRAD (F=6.22, p=.014) and UD (F=6.01, p=.016) groups and on mental QOL in the UD group (F=24.54, p<.000).Conclusion: Physical and depressive symptoms should be considered together to improve the QOL in women with rectal prolapse. Nursing interventions to decrease rectal prolapse-related physical and depressive symptoms are required to improve QOL in women with symptomatic rectal prolapse.