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Background This experimental study determined the in vitro, in vivo, and toxicity effects of Cinnamomum zeylanicum methanolic extract (CZME) against Toxoplasma gondii infection. Methods The in vitro activity of CZME T. gondii tachyzoites was studied by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Infected mice were treated with CZME for two weeks at doses of 20, 40, and 60 mg/kg/day. Then, the therapeutic effects of CZME were evaluated by assessing the mean number and mean size of T. gondii tissue cysts, oxidant-antioxidant enzymes, pro-inflammatory cytokines, and mRNA expression levels of bradyzoite surface antigen 1 (BAG1) by real-time PCR. Results CZME significantly (p <0.001) increased the mortality rate of parasites in a dose- and time-dependent response. The mean number of intracellular tachyzoites was significantly reduced after CZME therapy. The treatment of infected mice with CZME resulted in a significant (p <0.001) downregulation of BAG1 and the level of lipid peroxidation (LPO) and nitric oxide (NO) as oxidative stress markers. However, a considerable rise (p <0.05) was found in the levels of antioxidant markers such as glutathione peroxidase (GPx), catalase enzyme (CAT), and superoxide dismutase enzyme activity (SOD). In a dose-dependent response, after treatment of infected mice with CZME, the level of pro-inflammatory cytokines of IFN-γ, IL-1β, and IL-12 was considerably elevated. CZME had no significant cytotoxicity on Vero cells, with a 50% cytotoxic concentration of 169.5 ± 5.66 μg/ml. Conclusion The findings confirmed the promising therapeutic effects of CZME on chronic toxoplasmosis in mice. Nevertheless, further investigations must confirm these results, elucidate its precise mechanisms, and examine its effectiveness in human volunteers.