Background: Evaluation of herbs has been in progress worldwide for several decades to identify effective and safe substances for fertility regulation. This approach proved to be a good alternative to synthetic drugs as the chemicals of plant origin have limited side effects. Various medicinal plant extracts were investigated for their antifertility activity in female animal models. Aim of the work: This study was designed to investigate the toxic effects of Aloe barbadensis and Salvadora persica (Miswak) Mixture sap and to assess them as a contraceptive therapy. Material and Methods: Twenty female adult albino rats (Sprague dawley strain) were used in this study. Rats were divided into two groups (10 rats in each group); Group I (control untreated group) and Group II (mix treated group). Mixture of Aloe barbadensis and Miswak sap was orally administered (7 mg of Miswak + 7 mg of Aloe per 100 gram body weight) for 30 ± 2 days, where females were in the diestrus phase). All animals were decapitated after 30 days and blood samples were analyzed for estrogen, progesterone, tumor markers CA-15.3 and CA-125, kidney and liver functions, proteins profile and lipids profile. Results: The mean serum level of estrogen was significantly increased (p<0.01), while that of progesterone was significantly decreased (p≤0.01), in the Aloe barbadensis and Miswak group when compared to the control group. No significant difference was found between the treated and control groups for the serum level of tumor markers CA-15.3 and CA-125. Also, no significant difference was found between the two groups regarding kidney and liver function tests and proteins profile. The results also showed marked significant decline (p<0.01) in levels of the serum total lipids, total cholesterol, triglycerides, and LDL-cholesterol (LDL-C) in the treated group when compared to the control group. While, there was a significant elevation in HDL-cholesterol (HDL-C) level in the mix group when compared to the control group. Conclusion: It could be concluded that Aloe barbadensis and Miswak extract can be used as a safe contraceptive therapy that can increase the estrogen level due to its phytoestrogen components such as beta sitosterol, without deleterious effects on the vital organs (liver and kidneys).