Background: Women with gynecological cancer often experience psychological distress, particularly in response to surgical procedures. The impact of mandala art therapy (MAT) during the perioperative period for gynecological cancer patients remains uncertain. We aimed to examine the effects of the MAT program in women with gynecological cancer. Methods: Employing a quasi-experimental design, we recruited 126 gynecological cancer patients from a university hospital through convenience sampling. Participants were assigned to either receive the MAT program or standard perioperative care. The interventions comprised a three-session MAT program guided by a team of trained mandala psychologists. Generalized estimating equations (GEE) were employed to analyze the effects of MAT over time. Results: A total of 126 patients were enrolled, and 118 completed the entire study. Over 90% of participants completed the perioperative MAT interventions, reporting relatively high satisfaction with the program (7.70 out of 10). Individuals in the MAT group exhibited improved therapeutic effects on STAI-S, VASS, and vital signs over time. Notably, significant group*time interaction effects were noted in STAI-S scores at both the first evaluation, T1 (β = −4.220, P < .005) and the third evaluation, T3 (β = −3.797, P < .05), and VASS scores at T1 (β = −11.186, P < .005), T2 (β = −9.915, P < .05) and T3 (β = −9.831, P < .05). Regarding vital signs, the multivariate GEE model revealed significant interaction effects in systolic blood pressure values at both T1 (β = −7.102, P < .05) and T3 (β = −10.051, P < .005), diastolic blood pressure values at T3 (β = −6.441, P < .005), and pulse values at T1 (β = −6.085, P < .005). No significant differences were observed between groups for pain, hope, or self-acceptance. Conclusion: This study posited that MAT could serve as a valuable complementary approach in perioperative care for addressing the psychological needs of women with gynecological cancer. Subsequent research employing more robust methodologies and larger, more diverse participant samples will be necessary to validate these conclusions.