PURPOSE: In the present work, a group of nine medicinal plants (Sonchus oleraceus, Echinops spinosissimus, Trichodesma africana, Pergularia tomentosa, Teucrium oliverianum, Blepharis ciliaris, Citrllus colocynthis, Cleome amblyocarpa and Aerva javanica) from eight different families were investigated for their in vitro anti-leishmanial activity against the promastigote and amastigote stages of Leishmania major. L. major is the causative agent of cutaneous leishmaniasis (CL) which is one of the major health problems in Saudi Arabia and neighboring countries such as Iraq and Iran. However, the commonly available commercial therapeutics still come with multiple unwanted side effects in addition to parasite resistance, so medicinal plants have attracted attention due to their affordability and beneficial effects. METHODS: The selected plants were collected from Al Qassim region in the middle of Saudi Arabia, and then extracts were prepared with methanol using overnight soaking for the whole plants. RPMI 1640 was used to culture L. major to obtain promastigotes and intramacrophage amastigotes, which were used later for evaluation of extract activity in vitro via spectrophotometric and microscopic techniques. The MTT assay was used for cytotoxic evaluation of plant extracts against macrophage cells. Data were expressed in mean ± SD. Linear regression was used for IC and CC calculation. T test was used for significant differences at P ≤ 0.05. RESULTS: All the plants revealed anti-leishmanial activity against the L. major amastigote stage with IC values less than 91 µg/mL. The three most potent were T. oliverianum, P. tomentosa and C. amblyocarpa with IC values of 7.8, 13.7 and 21.5 µg/mL, respectively. The L. major promastigote stage was more tolerant, so only T. oliverianum extract showed an IC less than 30 (26.6 µg/mL). P. tomentosa is the most toxic plant with CC 3.1 µg/mL followed by T. africana CC 9.5 µg/mL, the other plants possess CC over 40 µg/mL. The best SI values were obtained from the C. amblyocarpa and T. oliverianum extracts against the L. major amastigote stages with 5.7 and 5.3, respectively. CONCLUSION: We can conclude that T. oliverianum, P. tomentosa and C. amblyocarpa are the best anti-leishmanial plants, so further phytochemical studies for isolation of active ingredients are highly recommended.