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Purpose: Cryptosporidium parvum is a protozoan parasite infecting most mammalian hosts and causing major health issues. The present study investigated the efficacy of ginger (Zingiber officinale), garlic (Allium sativum), and pomegranate (Punica granatum) peel extracts on the development and progression of experimental cryptosporidiosis in mice., Methods: Eighty-two mice were assigned to 6 groups: control, infected non-treated, metronidazole (MTZ), ginger, garlic, and pomegranate. The control group topically received no treatments. The infected non-treated group was experimentally infected by 10 4 C. parvum oocysts per mouse using a stomach tube. The MTZ group was infected with C. parvum oocysts combined with MTZ (50 mg/kg b.w./day). The ginger, garlic, and pomegranate groups daily received different plant extracts at doses of 100 mg/kg BW, 50 mg/kg BW, and 3 gm/kg BW, respectively, followed by infection with C. parvum oocysts. All treatments were applied orally one day after the infection for continuous 30 days., Results: Histopathological and immunohistochemical examinations for P53 and caspase-3 expressions in stomach and spleen tissues showed that MTZ and garlic-treated mice had a more significant effect on infected mice., Conclusion: The garlic extract was found to exert a more pronounced effect on infected mice compared with the other treatments as well as to improve health. Garlic extracts, therefore, represent an effective and natural therapeutic alternative for the treatment of cryptosporidiosis with low side effects and without drug resistance., (© 2022. The Author(s).)