The aim of this study was devoted into molecular docking calculations to discover the potential antileishmania and antitoxoplasma activities of newly synthesized compounds obtained by applying a practical and simple method under microwave irradiation. All these compounds were tested in vitro for their biological activity against Leishmania major promastigotes, amastigotes, and Toxoplasma gondii tachyzoites. Compounds 2a, 5a, and 5e were the most active against both L. major promastigotes and amastigotes, with IC50 values of less than 0.4 μM mL–1. Compounds 2c, 2e, 2h, and 5d had a strong antitoxoplasma activity of less than 2.1 μM mL–1 against T. gondii. We can conclude that aromatic methyleneisoindolinones are potently active against both L. major and T. gondii. Further studies for mode of action evaluation are recommended. Compounds 5c and 5b are the best drug candidates for antileishmania and antitoxoplasma due to their SI values being over 13. The docking studies of compounds 2a-h and 5a-e against pteridine reductase 1 and T. gondii enoyl acyl carrier protein reductase reveal that compound 5e may be an effective antileishmanial and antitoxoplasma drug discovery initiative.