Three new proaporphine alkaloids, cissamaline (4), cissamanine (5), and cissamdine (6), along with two known compounds (2 and 3) were isolated from total tertiary alakloidal extracts of the leaves and stems of Cissampelos capensis. The new alkaloids were elucidated through comprehensive spectroscopic analysis, including 1 D, 2 D NMR and High-resolution LCMS. The in vitro MTT cytotoxicity was evaluated on Caco-2 cell lines, where all the isolated compounds exhibited cytotoxic effects at concentrations above 250 µM. © 2022 Informa UK Limited, trading as Taylor & Francis Group.