Toxoplasmosis is a worldwide infection caused by the obligate intracellular protozoan parasite Toxoplasma gondii. Some pyrimidine analogs were synthesized to be evaluated for their antitoxoplasma effects in animal experiments. Results were assessed by studying parasite density, estimation of serum Toxoplasma antigen, studying the ultrastructural changes of the parasite, and the histopathological changes of the affected organs and inhibitory activity for dihydrofolate reductase (DHFR) isolated from Cryptosporidium parvum. The result showed that 4 out of 12 synthesized compounds have promising antitoxoplasma potentials. The animals that received these four compounds showed statistically significant decrease in the mean number of the parasite count in the liver and the spleen when compared to the corresponding control group. Moreover, Toxoplasma antigen was very low or even absent in the serum of animals receiving these compounds. Light microscopic examination of the peritoneal exudates of animals receiving these compounds showed stoppage of movement and deformity in shape of the tachyzoites, whereas scanning electron microscopy revealed that the organisms had lost their crescent shape, with dimples and deep ridges on their surfaces. Very mild histopathological changes were noticed in liver, spleen, and lungs of the groups of animals receiving these compounds in comparison to the other groups. Thus, these compounds proved their effectiveness in eradication of the experimental Toxoplasma infection and inhibition of DHFR from C. parvum.