Background: Portulaca oleracea (PO) is a widely known plant utilized for its medicinal attributes in the treatment of different illnesses. Objective: To investigate the effect of methanolic extract of PO (MEPO) on ovariectomy-induced reproductive toxicity in normal cyclic rats. Materials and Methods: Twenty 10-wk-old normal cyclic rats weighing 110-200 g were randomly divided into four groups (n = 5/group). Group A served as the control and received distilled water only. Group B was ovariectomized without treatment, while groups C and D were ovariectomized but treated with 400 and 800 mg/kg of MEPO, respectively, for 14 days. At the end of the experiment, body weight, serum hormonal levels, and estrous cycles were monitored across the groups. Results: Groups B, C, and D showed estrous cycle dysregulation and specific phase arrest when compared with the control. While a significant decrease in estradiol (p ≤ 0.001) and testosterone levels (p ≤ 0.001) were observed in groups B, C, and D, only groups C and D showed a significant increase in progesterone level when compared with the control (p ≤ 0.001, p = 0.01, respectively). Conclusion: The administration of 400 and 800 mg/kg MEPO is ineffective in ameliorating estrous cycle disruption and hormonal changes seen in ovariectomized normal cyclic adult Wistar rats. Key words: Portulaca oleracea, Wistar rat, Ovariectomy, Estrous cycle, Hormones.