Key message The natural durability of Dicorynia guianensis Amsh ’s heartwood is conferred by the high content of antioxidant phenolic compounds, especially tannins and flavonoids combined with the presence of fungistatic alkaloids. The content of phenolic compounds increases according to the natural durability classes, from durable wood (class 2) to moderately durable wood (class 3) and correlated to the antioxidant capacity. Context. The heartwood of Dicorynia guianensis Amsh is resistant to white rot fungi decay, but the mechanism of this natural durability is not fully elucidated. Aims. Biochemical studies were carried out in order to better understand the role of extractives in natural durability of D. guianensis. Methods. The powders from durable and moderately durable heartwood were extracted with methanol, ethanol, and hot water. The quantity of total phenols, tannins, and flavonoids as well as antioxidant activity, evaluated by 2,2′-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) were determined using colorimetric methods. Antifungal activity was assessed by using two white rot fungi. The bioactive fractions and compounds were obtained using bio-guided fractionation, HPLC isolation, MS and RMN spectroscopic analyses. Results. Durable woods contain higher amounts of heartwood extract and antioxidant activity. Antioxidant activity was highly correlated with the content of phenolics. The purification of the most antioxidant fraction FII affords the characterization of (+)-catechin (−)-epicatechin, neoastilbin, astilbin, and isoastilbin. Alkaloid fraction FIII exhibits dose-dependent fungistatic activity against Pycnoporus sanguineus Linnaeus and Trametes versicolor Quelet. Conclusion. Phenolic antioxidants and fungistatic alkaloids positively impact the natural durability of D. guianensis.