Duloxetine Hydrochloride is one of the most abundant antidepressants among Serotonin-Norepinephrine Reuptake Inhibitors. It is endorsed for treating Major Depressive Disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, and fibromyalgia. Our study aims to evaluate the implications of duloxetine hydrochloride on the reproductive health of female Wistar rats by measuring oxidative stress markers, histopathological alterations in reproductive tissues, and serum reproductive hormones, besides assessing the genotoxicity of duloxetine on female rats' reproductive organs using the comet assay. We conducted this study on 16 female Wistar rats divided into 2 groups; the control group; was administered distilled water, while the treated group; was administered 6.1 mg/kg of Duloxetine for a month. The results indicated a significant elevation in lipid peroxide Malondialdehyde and a significant decrease in reduced glutathione levels. A hormonal imbalance was evidenced by a reduction in estrogen levels, while Follicle-Stimulating Hormone (FSH) levels dramatically raised. Pathogenic morphological changes appeared in the reproductive tissues of the treated group compared to the control group. Moreover, significant DNA damage in the uterus and ovaries tissues of the treated group was revealed by the comet assay. Our results suggest cumulative damage may be produced by duloxetine due to its oxidative stress induction potency.