•Kaurane diterpenoids, fatty acids and sterols are the major lipophilic families.•Kaurenoic acid is the most abundant compound (554–1350mgkg−1 of dry mesocarp).•Cherimoya mesocarp shows several galloylated and non-galloylated flavan-3-ols.•‘Mateus I’ and ‘Mateus III’ cultivars have the highest phenolic contents.•Cherimoya fruit is a rich source of valuable phytochemicals in human diet and health. The lipophilic and phenolic extractives of the ripe mesocarp of four cherimoya cultivars (‘Perry Vidal’, ‘Mateus I’, ‘Mateus III’ and ‘Funchal’) from Madeira Island, were studied for the first time. The predominant lipophilic compounds are kaurene diterpenes (42.2–59.6%), fatty acids (18.0–35.6%) and sterols (9.6–23.7%). Kaur-16-en-19-oic acid is the major lipophilic component of all cultivars accounting between 554 and 1350mgkg−1 of dry material. The studied fruits also contain a high variety of flavan-3-ols, including galloylated and non-galloylated compounds. Five phenolic compounds were identified for the first time: catechin, (epi)catechin-(epi)gallocatechin, (epi)gallocatechin, (epi)afzelechin-(epi)catechin and procyanidin tetramer. ‘Mateus I’ and ‘Mateus III’ cultivars present the highest content of phenolic compounds (6299 and 9603mgkg−1 of dry weight, respectively). These results support the use of this fruit as a rich source of health-promoting components, with the capacity to prevent or delay the progress of oxidative-stress related disorders.