Cryptosporidium is a protozoan that can result in severe diarrhea which is usually self-limiting in immunocompetent individuals but may be chronic and life threatening to those who are immunocompromised. Aim of the work to study the effect of silver nanoparticle (AgNps) - loaded nitazoxanide (NTZ) in treatment of cryptosporidiosis in the experimentally infected immunocompetent and immunosuppressed mice. Methods is the study included two major groups of immunocompetent and immunosuppressed mice. Each group had the following subgroups; normal control, infected control, infected treated with nitazoxanide, infected treated with silver nanoparticle, infected treated silver nanoparticle- loaded nitazoxanide 100ug/g and infected treated silver nanoparticles loaded nitazoxanide 200ug/g. Mice were subjected to stool examination for oocysts count and were later sacrificed for organs dissection, histopathological examination of intestinal tissue and assessment of the toxicity of silver nanoparticles in mice tissues. Also, immunological assessment of circulating cytokines (IFN-γ, IL-4, IL-10 and IL17) in the serum of the mice was done. The results revealed that the silver nanoparticle loaded nitazoxanide (200ug/g) showed the lowest number of oocysts shedding and the highest improvement of histopathological changes with a remarkable decrease in all of the immune mediators in both immunocompetent and immunosuppressed mice. No tissue toxicity in all silver nanoparticles treated mice. Conclusion AgNps loaded NTZ proved its effectiveness against the experimental cryptosporidiosis than nitazoxanide alone.