Toxoplasmosis constitutes a global infection caused by oblige intracellular apicomplexan protozoan parasite Toxoplasma gondii. Although often asymptomatic, infection can result in more severe, potentially life threatening symptoms particularly in immunocompromised individuals. The present study evaluated the anti-Toxoplasma effects in experimental animals of silver nanoparticles synthesized in combination with extracts of natural plants (Phoenix dactylifera and Ziziphus spina-christi) as an alternative method to standard sulfadiazine drug therapy. Liver functions estimated by and AST and ALT were significantly increased in T. gondii-infected mice compared with the control group as well as hepatic nitric oxide (NO), lipid peroxidation (LPO) levels and caused significant decrease in superoxide dismutase (SOD), catalase (CAT) and glutathione activities in the liver homogenates. Nanoparticles pretreatment prevented liver damage as determined by enzyme activity inhibition, in addition to significant inhibition of hepatic NO levels and significant elevation in liver SOD and CAT activities. Moreover, nanoparticle treatment significantly decreased hepatic LPO and NO concentrations and proinflammatory cytokines but significantly boosted the antioxidant enzyme activity of liver homogenate. In addition, histological examinations showed distinct alterations in the infected compared with untreated control groups. Conversely, nanoparticles pretreatment showed improvement in the histological features indicated by slight infiltration and fibrosis, minimal pleomorphism and less hepatocyte and degeneration. Furthermore, nanoparticles treatment induced a reduction in immunoreactivity to TGF-β and NF-κB in hepatic tissues. Therefore, the present study provides new insights into various natural plants that are used traditionally for the treatment of toxoplasmosis and other parasitic infections, which may be useful as alternative treatment option for T. gondii infections.