INTRODUCTION: Women with type 2 diabetes mellitus (T2DM) have an increased risk of ovarian cancer. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) impact on the risk of ovarian cancer in women with T2DM remains unclear. Therefore, this study aims to assess the association between SGLT2i use and the risk of ovarian cancer in patients with T2DM. METHODS: We conducted a retrospective cohort study using the TriNetX network between January 2013 and December 2023. We employed a new-user study design with an active comparator, comparing patients using dipeptidyl peptidase-4 inhibitors (DPP4i). Propensity score matching (PSM) was applied to balance baseline characteristics. The primary outcome was the incidence of ovarian cancer. RESULTS: Following PSM, 92,090 patients were included in each group. The SGLT2i gorup was associated with a significantly lower risk of ovarian cancer compared to the DPP4i group (HR: 0.758, 95 % CI: 0.596-0.965). Subgroup analyses revealed a consistent trend across various populations, with a notably significant risk reduction observed in white patients (HR: 0.667, 95 % CI: 0.485-0.917). CONCLUSIONS: Our study suggests that SGLT2i may be associated with lower risk of ovarian cancer in T2DM patients. These findings highlight the need for further investigation into the underlying mechanisms.