Cutaneous leishmaniosis is an important zoonotic disease caused by various Leishmania species. The aim of this study was to investigate the effects of silibinin and silymarin on the in vitro growth and proliferation of promastigotes and amastigotes of Leishmania major compared to glucantime-treated parasites. The promastigotes and amastigotes of this parasite were treated with the two drugs, silibinin and silymarin, in several concentrations (25–100 μM). The highest effect on promastigotes was for silymarin in concentration of 100 μM with 90% and 91% death rate at hours 48 and 72, respectively. Regarding amastigotes, the highest effect at 48 hours was for silibinin in concentration of 100 μM with 35% death rate. However, at 72 hours, silymarin showed the highest effect with 63% death rate in concentration of 100 μM. The highest observed maximal 50% lethal concentration (LC50) for promastigotes was for silymarin with 19.34 μM at 48 hours and 18.22 μM at 72 hours. Likewise, maximal LC50 for amastigotes was for silymarin with 191 μM at 48 hours and 24.27 μM at 72 hours. Our findings demonstrated that both medications have suitable effects like Glucantime® on the parasite in vitro. Therefore, clinical assessment of the anti-leishmanial activity of silibinin and silymarin for treating the dermal lesions caused by L. major is recommended.