Background and study aim: Toxoplasma gondii (T. gondii) is a worldwide distributed obligate intracellular protozoan. Oxidative stress is the main mechanism of the host's defense against protozoan infection. It has an essential role throughout Toxoplasma infection in the host and the parasite and is proposed to participate in the mechanism of neuropathology and neurodegeneration. At present, treatment of toxoplasmosis is not optimal. The current work aimed to assess the therapeutic and antioxidant indices of Lepidium sativum seeds extract (LSSE), eucalyptus leaf extract, olive leaf extract (OLE), and Resveratrol (RSV)against experimental toxoplasmosis. Patients and Methods: 176 male Swiss albino mice were divided into 11 groups. Animals were sacrificed 8 weeks post infection. The efficacy of tested drugs was evaluated using parasitological, biochemical, oxidants/ antioxidants parameters, total antioxidant capacity, and cytokines gene expression. Results: Natural plants (OLE, LSSE, Eucalyptus) and RSV showed anti toxoplasma effect via reducing the brain cysts count, hepato-renal protective activity through reducing ALT, AST, urea, and creatinine as well as a significant antioxidant potential through increasing levels of TAC, GSH, catalase, and decreasing levels of MDA and NO either when used as a monotherapy or combined with pyrimethamine and sulfadiazine. Additionally, olive leaf extract showed an anti-inflammatory effect through decreasing the pro inflammatory cytokine IL1β besides increasing the anti-inflammatory cytokine IL-10. Conclusion: In conclusion, natural plants mainly olive leaf extract and Lepidium sativum can be promising sources for anti Toxoplasma medications.