A pair of new isomeric indole alkaloids, naucleaorals A (1) and B (2) were isolated from the roots of Nauclea orientalis. The structures of compounds 1 and 2 were fully characterized using spectroscopic data, and were tested for their cytotoxicity (HeLa and KB cells) and antimalarial activity. Compound 1 showed significant cytotoxicity to HeLa cells with an IC(50) value of 4.0 µg/mL, while compound 2 exhibited very modest cytotoxicity to both cell lines with IC(50) values of 7.8 and 9.5 µg/mL, respectively. Both compounds proved to be inactive in antimalarial assays (IC(50)>10.00 µg/mL).