Background: Since current therapies for toxoplasmosis are only effective against tachyzoites in acuteinfections, and the occurrence of drug resistance, researches are directed to use natural products in thetreatment of chronic toxoplasmosis.Objective: To investigate the potential efficacy of metal-organic framework (MOF) loaded coconut oil(CO) and ginger oil (GO) nanoparticles (NPs) in the treatment of chronic murine toxoplasmosis.Material and Methods: Ninety laboratory bred Swiss Albino mice were divided into 8 groups (10 miceeach); GI (negative control), GII (infected control), GIII-GVIII (infected with Me49 strain of T. gondiiand treated with MOFs-NPs, Spiramycin, Spiramycin loaded on MOFs-NPs, CO-MOF-NPs, GO-MOF-NPs,and CO+GO-MOFs-NPs, respectively). Parameters used for evaluation included brain cyst count, tissuepathology, and CD8+ infiltration of the liver.Results: A statistically significant difference was observed in the number of brain cysts between allinfected groups receiving treatment, and GII; and GV showed the lowest count of brain cysts with a 60.8%reduction. Histopathological examination showed that loading CO and GO separately or combined withMOFs-NPs significantly restored the normal architecture of all examined tissues, i.e., brain, eye, liver, andkidney. Using immunohistochemical (IHC) staining, high-density CD8+ infiltration was recorded in theliver section of both GI and GII. While GIII, GIV, and GVI displayed low-density CD8+ infiltration, GV, GVII,and GVIII showed intermediate-density.Conclusion: Loading on MOFs-NPs, CO, and GO offered promising phytotherapy against chronictoxoplasmosis.