In this study, the potential anti-cryptosporidial effect of Nigella sativa (black seeds) and Zingiber officinale (ginger) alcoholic extracts versus Nitazoxanide (NTZ) medication was investigated in immunosuppressed (IS) laboratory mice. Parasitological, histopathological studies were used to assess their therapeutic efficacy. Serum level and tissue expression percentage of IFN-γ was also used. Nigella extract succeeded to reduce the mean oocyst counts in the feces of immunosuppressed mice followed by NTZ. Ginger-treated ones showed the lowest reduction percentage. Nigella sativa showed the best results in terms of restoring the normal architecture of ileal epithelium in histopathological sections stained with H&E. NTZ treatment sub-groups showed mild improvement, followed by ginger-treated mice, which showed a slight improvement in small intestine microenvironment. A significant substantial rise in serum and intestinal tissue IFN-γ cytokine levels were recorded in Nigella subgroups compared to those of NTZ and ginger respectively. According to our findings Nigella sativa outperformed Nitazoxanide in terms of anti-cryptosporidial effectiveness and regeneration characteristics revealing a promising medication. When compared to the commonly used Nitazoxanide medication or Nigella extracts, the outcomes of ginger extract were suboptimal.