Background Apicomplexa is a phylum of single-celled, obligate intracellular protozoan parasites that are among the most common morbidity-causing diseases worldwide. This phylum contains a variety of intestinal protozoa of medicinal and veterinary interest, such as Cryptosporidium and Toxoplasma. These parasites can be acquired orally, before infecting or infiltrating the intestinal epithelium. Nitazoxanide (NTZ) is the only FDA-approved medicinal therapy currently in use. The conventional pharmacological therapies for toxoplasmosis include pyrimethamine and sulfadiazine; nevertheless, they have major limitations. The use of medicinal plants for treatment and to reduce dependence on chemical drugs has become an important goal for therapeutic research. bjective Intending to develop alternative therapeutic options to address these health problems, we examined the efficacy of an ethanol extract of Cyperus rotundus, which has been demonstrated to have antiparasitic and hepatoprotective effects against Cryptosporidium and Toxoplasma in mice, with the goal of developing alternative therapeutic options to treat these health problems. Materials and methods A total sample of 72 male mice was used for the experiment, the animals were separated into two groups of 36 mice each: the first group was used to examine the activity of ethanol extract of C. rotundus against Cryptosporidium, and the second group was used to examine its activity against Toxoplasma. Each experimental model was divided into six subgroups of six mice each: the first group was noninfected nontreated, the second infected nontreated, third infected and treated with the standard drug, fourth and fifth infected and treated with C. rotundus at 250 and 500mg/kg body weight, respectively, and the sixth infected and received a combination of half doses of both drugs [C. rotundus (250mg/kg/day) and half dose of the standard drug (NTZ or Spiramycin)]. The parasitological parameters and reduced glutathione, super oxide dismutase, and malondialdehyde levels in the liver homogenates were used to determine the infections and medication impacts. Results and conclusion The results showed a promising finding that ethanol Egyptian herbal extract of C. rotundus and its combination with the standard drugs NTZ and Spiramycin have a promising antiparasitic and hepatoprotective activity against murine cryptosporidiosis and toxoplasmosis, respectively. The combined therapies resulted in the highest effectiveness of standard medications.