Introduction: Leishmaniasis is an infectious disease caused by Leishmania, a protozoa parasite. This disease reaches millions of people annually around the world. The treatment of leishmaniasis takes into account the clinical form of the disease, the host and the parasite. However, restricted access to diagnosis and medication and low adherence makes it difficult to control the disease. Thus, more efficient drugs are need and natural products can be a good alternative. Iridoids are natural products with leishmanicidal activity reported in the literature. Therefore, these compounds can be exploited for the development of anti-Leishmania drugs. Objective: In this study, molecular modeling studies of five isolated iridoids, asperuloside and geniposide from Escalonia bifida, galiridoside from Angelonia integerrima and theveridoside and ipolamiide from Amphilophium crucigerum, and those cited in the literature as active against Leishmania spp. were performed. Methods: For the experiments aerial parts of Escallonia bifida Link & Otto (Escalloniaceae), Angelonia integerrima Spreng (Plantaginaceae) and Amphilophium crucigerum (L.) L.G. Lohamn (syn. Pithecoctenium crucigerum) (Bignoniaceae) were collected in Rio Grande do Sul, in the cities of Taquara, Santo Antonio da Patrulha and Nova Santa Rita, respectively, Brazil. The species were identified by the botanist Dr. Sérgio Augusto de Loreto Bordignon (UNILASALLE, RS, Brazil). The plant material was subjected to maceration exhaustively with ethanol (99.5 °GL) and was concentrated in a rotary evaporator (40-60 °C). The ethanolic extract was subjected to liquid-liquid extraction with diethyl ether (1:2 v/v), and the aqueous fractions were submitted to column chromatography on silica gel 60 (Acros Organics; 0.060-0.200 mm) affording five compounds which structures were elucidated by nuclear magnetic resonance (NMR Varian 400 MHz MR 400) of 1H, 13C, correlation. Physicochemical parameters of the isolated molecules and of those described in the literature were achieved by using the software Volsurf+ and the SwissADME web server. The pharmacophore hypothesis was built through the alignment of 10 structures from literature, compound a, compound b, compound c, catapol, 3,4-dihydro-6-O-methylcatalpol, ajugoside, ajugol, 6-O-β-D-xylopyranosylaucubin, aucubin, 6-O-methylcatapol, by THESEUS alignment algorithm available in YASARA [6] demo version and the pharmacophoric features were set manually using the Discovery Studio Visualizer 4.0. Results and Conclusion: The physicochemical parameters predicted for the isolated iridoids did not show differences compared to those described in the literature. The SAR and the pharmacophoric model confirmed the importance of maintaining the cyclopentane[C]pyran ring of the iridoid, of oxygen-linked substituents at the C1 and C6 positions and of bulky substituents attached to the iridoid ring to present leishmanicidal activity.