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Abstract Objective Toxoplasma gondii, an intracellular zoonotic parasite, infects approximately a third of the world population. Current drugs for treatment of T. gondii infection have been challenged with ineffectiveness and adverse side effects. This necessitates development of new anti-Toxoplasma drugs. Sorghum bicolor [Moench] leaf extract has been used in African traditional medicine for the management of anemia and treatment of infectious diseases. We tested the in vitro anti-Toxoplasma inhibitory activity of S. bicolor’s oil-like crude extracts and fractions against T. gondii and determined their cytotoxic effects on human host cells. Results Significant inhibitory activities against the growth of T. gondii tachyzoites were observed for the crude extract (IC50 = 3.65 µg/mL), the hexane-methanol fraction (IC50 = 2.74 µg/mL), and the hexane fraction (IC50 = 3.55 µg/mL) after 48 h of culture. The minimum cytotoxicity concentrations against HFF were 34.41, 16.92 and 7.23 µg/mL for crude extract, hexane-methanol and hexane fractions, respectively. The crude extract and fractions showed high antiparasitic effects with low cytotoxic effects. Further studies to determine synergistic activities and modes of action would provide impetus for the development of new toxoplasmosis drugs or nutraceuticals.