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<p>Abstract</p> <p>Background</p> <p>Worldwide particularly in developing countries, a large proportion of the population is at risk for tropical parasitic diseases. Several medicinal plants are still used traditionally against protozoal infections in Yemen and Saudi Arabia. Thus the present study investigated the <it>in vitro</it> antiprotozoal activity of twenty-five plants collected from the Arabian Peninsula.</p> <p>Methods</p> <p>Plant materials were extracted with methanol and screened <it>in vitro</it> against erythrocytic schizonts of <it>Plasmodium falciparum</it>, intracellular amastigotes of <it>Leishmania infantum</it> and <it>Trypanosoma cruzi</it> and free trypomastigotes of <it>T. brucei</it>. Cytotoxic activity was determined against MRC-5 cells to assess selectivity. The criterion for activity was an IC₅₀ < 10 μg/ml (<5 μg/ml for <it>T. brucei</it>) and selectivity index of >4.</p> <p>Results</p> <p>Antiplasmodial activity was found in the extracts of <it>Chrozophora oblongifolia</it>, <it>Ficus ingens</it>, <it>Lavandula dentata</it> and <it>Plectranthus barbatus</it>. Amastigotes of <it>T. cruzi</it> were affected by <it>Grewia erythraea</it>, <it>L. dentata</it>, <it>Tagetes minuta</it> and <it>Vernonia leopoldii</it>. Activity against <it>T. brucei</it> was obtained in <it>G. erythraea</it>, <it>L. dentata</it>, <it>P. barbatus</it> and <it>T. minuta</it>. No relevant activity was found against <it>L. infantum</it>. High levels of cytotoxicity (MRC-5 IC₅₀ < 10 μg/ml) and hence non-specific activities were noted in <it>Cupressus sempervirens</it>, <it>Kanahia laniflora</it> and <it>Kniphofia sumarae</it>.</p> <p>Conclusion</p> <p>The results endorse that medicinal plants can be promising sources of natural products with antiprotozoal activity potential. The results support to some extent the traditional uses of some plants for the treatment of parasitic protozoal diseases.</p>