An aqueous decoction (dried extract), an 80 % methanolic extract from Morinda morindoides (Rubiaceae) leaves, and five iridoids isolated from the 80 % methanolic extract were evaluated in vitro for their activity against Entamoeba histolytica and their cytotoxicity. The aqueous decoction and the 80 % methanolic extract exhibited a promising antiamoebic activity with IC50 values of 3.1 ± 1.7 and 1.7 ± 0.6 μg/mL, respectively. All tested iridoids displayed antiamoebic activity, the most active being epoxygaertneroside (IC50: 1.3 ± 0.4 μg/mL) and methoxygaertneroside (IC50: 2.3 ± 0.7 μg/mL) followed by gaertneroside, acetylgaertneroside and gaertneric acid with IC50 values of 4.3 ± 1.8, 5.4 ± 1.4 and 7.1 ± 1.4 μg/mL, respectively. Synergistic effects between the iridoids tested, or with other constituents, may explain the high activity of the extracts. All extracts and iridoids were devoid of any cytotoxic effect against MT-4 cells at the highest test concentration of 250 μg/mL. These findings support at least in part the traditional use of Morinda morindoides leaves for the treatment of amoebiasis in the Democratic Republic of Congo.