Background Conventional treatment for toxoplasmosis have severe side effects and the inability to completely eradicate the disease. Therefore, the acquisition of new anti- Toxoplasma drugs has always been of interest among researchers. In the present study, we prepare a new indole-triazole derivatives and evaluated their potential anti-parasitic activity against tachyzoites of Toxoplasma RH strain. Materials and methods In this study, after synthesis of the two new compounds of indole-triazole, the effect of their different concentrations (2–1024 μg/ml) were determined on Toxoplasma tachyzoites using flow cytometry. Furthermore, tachyzoites were exposed to different concentrations of compounds (4, 16, 64, 265, 1024 μg/ml) for 1.5 h and their infectivity were evaluated in BALB/c mice. Results The flow cytometry results indicated the benzyl derivative of indole-triazole in various concentrations had a lethal effect on tachyzoites between 11.93% and 89.66%, while the naphthalene derivative had a lethality of 26.63%–66.82%. The infectivity analysis showed that the survival time of mice at concentrations of 1024 μg/ml and 512 μg/ml of benzyl derivatives was significantly increased ( P = 0.008 and P = 0.016, respectively), compared to that in the negative control group. Furthermore, survival time of mice was statistically significant at the concentration of 1024 μg/ml for naphthyl derivative ( P = 0.012). Conclusion Findings of the current study suggested indole triazole compounds, based on their structure and enzymes targeting, have a considerable effect on tachyzoites of T. gondii RH strain and can be considered as a new anti- Toxoplasma agent.