Cryptosporidium parvum (C. parvum) is an intestinal parasite that infects immunosuppressed and immunocompetent people. Cryptosporidiosis is the second largest cause of diarrhea and mortality in children after rotavirus. Nitazoxanide (NTZ) has limited activity in immunocompromised individuals thus, it is increasingly necessary for evaluating new potential drugs against Cryptosporidium in immunosuppressed patients. The current research aimed to investigate the efficiency of Lactoferrin (LF) and Silver Nanoparticles (AgNps), separately, against C. Parvum infection in immunosuppressed mice in comparison with nitazoxanide and to study the effect of their combination on parasitological and histopathological changes. Oocyst output showed that shedding in mice treated with LF, AgNps, and NTZ combination was lower than NTZ treated one. Histopathological examinations of the infected mice treated by NTZ, LF, and AgNps in the intestine showed a regular villous pattern with no evidence of inflammatory changes. The section in the lung tissue showed no apparent pathological changes. Also, the toxicity in mice treated with LF, AgNps, and NTZ combination was lower than NTZ treated one. The combined treatment of NTZ, LF, and AgNps resulted in the highest decrease in Cryptosporidium oocyst number compared to the other treatments tested. Lactoferrin is used as an adjuvant alongside other similar medications to treat cryptosporidiosis.