Leishmaniasis and toxoplasmosis are parasitic protozoal diseases that pose serious health concerns, especially for immunocompromised people. Leishmania major and Toxoplasma gondii are endemic in Saudi Arabia and are particularly common in the Qassim Region. The present work was conducted to evaluate the in vitro antileishmanial and antitoxoplasmal activity of methanolic extracts and phytochemical fractions from two plants, Euphorbia retusa and Pulicaria undulata, which are ethnobotanical agents used to treat parasitic infection. Whole E. retusa and P. undulata plants were extracted with methanol and fractionated using petroleum ether, chloroform, ethyl acetate, n-butanol, and water and then were tested in vitro against L. major promastigote and the amastigote stages of T. gondii; the cytotoxicity of the extracts was tested against Vero cell line. The methanolic extracts of E. retusa and P. undulata exhibited promising antitoxoplasmal activity against T. gondii with EC50 values 5.6 and 12.7 μg mL-1 , respectively. The chloroform fraction of P. undulata was the most potent, exhibiting an EC50 of 1.4 μg mL-1 and SI value of 12.1. It was also the most active fraction against both L. major promastigotes and amastigotes, exhibiting an EC50 of 3.9 and 3.8 μg mL-1 and SI values 4.4 and 4.5, respectively. The chloroform fraction from P. undulata is a very good candidate for the isolation of active antitoxoplasmal and antileishmanial ingredients; therefore, further phytochemical analysis for active compound isolation is highly recommended.