This work describes the phytochemical study on Peltodon longipes with a focus on the search for bioactive compounds and their detailed in vitro biological investigation. Phytochemical studies afforded the isolation of twelve diterpenes from the abietane type. The diterpenes displayed remarkable cytotoxicity, especially 7alpha-acetoxyroyleanone, the major compound. Some of these diterpenes were tested for their alkylating properties; topoisomerase I and II relaxation activity; the ability to generate DNA-strand breaks in single cells using the alkaline comet assay and the ability of cells to recover from the DNA damage; their influence on cell cycle progression and arrested and the inhibition of the main CDK-cyclin complexes directly involved in driving the cell cycle. These studies on their cytotoxic activity revealed new insights in structure activity relationships and in the complex molecular mechanism. Depending on their functional groups, we propose that abietane diterpenes utilise different mechanisms to induce cell death.