A new alkaloid, manniindole1, together with four known compounds: aristolactam AII2, aristolactam BII3, piperolactam D4and polycarpol5were isolated from the crude extract EtOH-H2O (8:2) of the roots ofAnonidium manniiby chromatographic separation. The structure elucidation was performed on the basis of a spectroscopic analysis (IR, HRESI MS, 1D and 2D NMR) as well as a comparison of their spectral data with those reported in the literature. For the first time, the crude extract and those isolated compounds were evaluated for their anti-schistosomal activity againstSchistosoma mansoniand for cytotoxicity activity against Huh7 and A549 cells. Furthermore, they were also testedin vitroon the recent characterizedSchistosoma mansoniNAD(+)catabolizing enzyme (SmNACE) for their impact on this enzyme which is localized on the outer surface of the adult parasite. Compound2displayed quite good worm killing capability, while4showed significant inhibition ofSmNACE.