In a project aimed at searching for biogenetic intermediates of Daphniphyllum alkaloids, two novel alkaloids with a unique aza-adamantane core, daphnezomines A (1) and B (2), were isolated from the leaves of Daphniphyllum humile. Their structures, including relative stereochemistry, were elucidated using spectroscopic data and chemical methods, while the absolute configuration of 2 was established by X-ray crystallographic analysis. Composed entirely of six-membered rings, daphnezomines A (1) and B (2) are the first natural products containing an aza-adamantane core with an amino ketal bridge. Daphnezomine B (2) exhibited cytotoxicity against murine lymphoma L1210 and human epidermoid carcinoma KB cells in vitro with IC50 values of 0.46 and 8.5 µg/mL, respectively, whereas daphnezomine A (1) was not cytotoxic (IC50 > 10 µg/mL).