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Abstract Toxoplasmosis induced by Toxoplasma gondii is a well-known health threat, that prompts fatal encephalitis increased with immunocompromised patients, in addition, it can cause chorioretinitis, microcephaly, stillbirth in the fetus and even led to death. Standard therapy uses sulfadiazine and pyrimethamine drugs revealed beneficial results during the acute stage, however, it has severe side effects. UPLC-ESI-MS/MS used to explore C. limon MeOH ext. constituents, which revealed a list of 41 metabolites of different classes encompasses; unsaturated fatty acid, tricarboxylic acids, phenolic aldehyde, phenolic acids, phenolic glycosides, coumarins, sesquiterpene lactone, limonoid, steroid and flavonoids. C. limon MeOH ext. and the isolates reduced significantly the number of T. gondii tachyzoites. Consequently, histopathological examination, proved significant reduction in the number of mononuclear inflammatory cells in the kidney and liver sections, besides, lowering the number of shrunken and degenerative neurons in the brain sections of infected mice. Molecular docking study was performed targeted certain receptors, which are important for the life cycle fundamentals for the parasite mobility including invasion and egress, and further molecular dynamics simulation was conducted to get insights into the structural changes of the formed complexes, along with a pharmacophoric mapping approach, that confirmed the need for a free hydroxyl group and/or a phenolic substituted one, in order to form HB, Hyd/Aro and ML interactions, through which, cell cycle disruption via iron chelation, could be achieved. In addition, the ADMIT properties of all identified metabolites were predicted.