The efficacy of compound PPQ-8 combined with Nitazoxanide against Toxoplasma gondii was examined in a murine model infected with a non-virulent (Me49) strain. Thirty female Swiss- albino mice (6 weeks old) were inoculated by mouth with 20 cysts and divided into 3 groups. The first group was left untreated, the second group treated with Pyrimethamine and sulfadiazine (PYR/SDZ), while, the third one was treated with PPQ-8 and Nitazoxanide (PPQ-8/NTZ), treatment was started 4 days post-infection and continued for 14 consecutive days. Five mice from each group were sacrificed and the rest were observed for 30 days. Results showed that, the median survival duration of the untreated group was 3.66 weeks, while, that of PYR/SDZ and PPQ-8/NTZ groups were 3.86 and 3.77 weeks, respectively. The number and size of Toxoplasma cysts in brain were significantly decreased among PYR/SDZ and PPQ-8/NTZ-treated groups when compared with infected untreated group. Histopathological examination of brain of control mice showed severe inflammation while, mice treated with PYR/SDZ reported moderate inflammation and mice given PPQ-8/NTZ showed mild inflammation. PPQ-8/NTZ induced a significant increase in serum level of IFN-γ more than PYR/SDZ when compared with infected untreated group. Both PYR/SDZ and PPQ-8/NTZ-treated groups decrease of serum TNF-α level when compared with the untreated group. Conclusively, PPQ-8/NTZ combination shows promising results, hence it could be a potential combination used alternatively with PYR/SDZ for treatment of toxoplasmosis.