Cryptosporidium is a ubiquitous protozoan parasite causing gastrointestinal disorder in various hosts worldwide. The disease is self-limiting in the immunocompetent but life-threatening in immunodeficient individuals. Investigations to find an effective drug for the complete elimination of the Cryptosporidium infection are ongoing and urgently needed. The current study was undertaken to examine the anti-cryptosporidial efficacy of curcumin in experimentally infected mice compared with that of paromomycin. Oocysts were isolated from a pre-weaned dairy calf and identified as Cryptosporidium parvum using a nested- polymerase chain reaction (PCR) on Small subunit ribosomal ribonucleic acid (SSU rRNA) gene and sequencing analysis. One hundred and ten female BALB/c mice were divided into five groups. Group 1 was infected and treated with curcumin; Group 2 infected and treated with paromomycin; Group 3 infected without treatment; Group 4 included uninfected mice treated with curcumin, and Group 5 included uninfected mice treated with distilled water for 11 successive days, starting on the first day of oocyst shedding. The oocyst shedding was recorded daily. At days 0, 3, 7, and 11 of post treatments, five mice from each group were killed humanly; jejunum and ileum tissue samples were processed for histopathological evaluation and counting of oocyst on villi, simultaneously. Furthermore, total antioxidant capacity (TAC) and malondialdehyde (MDA) concentrations in affected tissues were also measured in different groups. By treatments, tissue lesions and the number of oocyst on villi of both jejunum and ileum were decreased with a time-dependent manner. In comparison with Group 3, oocyst shedding was stopped at the end of treatment period in both groups 1 and 2 without recurrence at 10days after drug withdrawal. Also, TAC was increased and the MDA concentrations were decreased in Group 1. Moreover, paromomycin showed acceptable treatment outcomes during experiment and its anti-cryptosporidial activity was faster than curcumin. The results confirmed the anti-cryptosporidial and antioxidant activity of curcumin against C. parvum and further evaluation of immunosuppressed animal models needs to be carried out.