The anti-inflammatory and antiproliferative activities of 4b-cinnamoyloxy,1b,3a-dihydroxyeudesm-7,8- ene (1) and of three derivatives, namely diacetate (2), hydrogenate (3) and diacetate hydrogenate (4) were evaluated. All derivatives exert an anti-inflammatory effect significantly lower than that exerted by 1. Otherwise, both the lead compound and 2–4 showed a comparable antiproliferative activity on human tumor cell lines. The investigation of the mechanism of action accountable for cytotoxicity high- lighted the capacity to impair mitochondrial functions through two different pathways, depending on chemical structure. In particular, the lead compound 1 and derivative 3 are able to induce mitochondrial permeability transition, while derivatives 2 and 4 inhibit Complex II in the respiratory chain.