Ethyl acetate and chloroform extracts from aerial parts of Portulaca werdermannii and P. hirsutissima were tested in lymphoproliferation assays and axenic cultures of Leishmania amazonensis and Trypanosoma cruzi. Both extracts of P. werdermannii and P. hirsutissima had a potent inhibitory activity on lymphocyte proliferation. On the contrary, only the chloroformic extract of both plants inhibited L. amazonensis growth, without effect on T. cruzi cultures. These results indicate these Portulaca species as potential sources of new active molecules for the treatment of leishmaniasis and immune-mediated pathologies