Phytochemical investigation of Nauclea latifolia Smith. (Rubiaceae), an African ethnomedicinal plant, yielded a new indolo[2,3-a]quinolizidine alkaloid, nauclealatimide (1), two previously unknown lignans named nauclealignan A (2) and B (3), as well rhemaneolignan B (4) and spicatolignan A (5) from the hydromethanolic extract obtained after ultrasonication of the stem bark. Their chemical structures were elucidated using IR, NMR (1D and 2D) and HRESIMS spectral evidence as well as comparisons with existing literature data.