Cryptosporidiosis is a zoonotic disease caused by a well-known parasitic protozoan called Infection in livestock causes important economic losses among farm animals and its control has a global concern. In this study, internal white and external red layers were separated from pomegranate peels () then; they were grinded to reach Nano form. Anticryptosporidial effect of their water extracts was investigated in experimentally infected mice. Also, their antioxidant activity, biochemical and histopathological changes were studied. Briefly, hot aqueous extracts of pomegranate peels were prepared regarding its good sensory attributes at concentration of 10% W/V. Analysis of total phenolics, individual phenolics by HPLC-DAD and antioxidant activities have been done. Forty-five mice were divided into five groups each one containing nine mice. The first group was healthy mice and the 2nd one was infected orally with 10 () oocysts/mice and not treated. The other 3 groups were infected and orally treated with Nitazoxanide (NTZ) for the 3rd group, pomegranate red peel extract for the 4th group and pomegranate white peel extract for the 5th group. Blood samples were collected after 1 and 2 weeks post treatment for protein profile, liver enzymes and antioxidant activity evaluation. After 3 weeks, all animals were sacrificed and ileal tissues were embedded in paraffin for histopathological examination. The results showed that pomegranate peel extracts were rich in phenolic compounds, had high antioxidant activity and therapeutic effect on in experimentally infected mice. Red peel extract diminished oocysts count significantly in experimentally infected mice than white peel and NTZ treatments. Also, the histopathological examination revealed that red peel treated mice ileal sections showed a great enhancement in the shape and structure of villi towards normal structure than other treated groups. Most of the measured biochemical parameters after 2 weeks' treatment with red pomegranate peel and NTZ were enhanced in their concentrations towards the healthy normal status. In conclusion, this study showed the effectiveness of Nano-form of pomegranate white and red peel extracts against oocysts. Pomegranate red peel extract was found to have antioxidant activity that could significantly enhance the serum biochemical parameters and oxidative stress towards the healthy normal status. Furthermore, it is suggested that pomegranate peel should be separated and used in the daily animal diet or as a functional beavarage for human as accepted from the panelists to give protective effects against this parasite as well as to improve health benefits.