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Phytochemical investigation of the stem bark of Trewia nudiflora led to the isolation of two new cardenolides, trewianin (1) and trewioside (2), along with scopoletin (3) and indole-3-carboxylic acid (4). Structures were established by 1D- and 2D NMR spectroscopy, HR-MS analysis, and by comparison with literature data.