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Guiana is a little-known and endemic variety of cocoa (Theobroma cacao L.), native to French Guiana. No data were available regarding its chemical composition and biological properties; therefore, a study was necessary, using Forastero as a reference. To exemplify biological activities of the cacao species, cocoa extracts were evaluated by antioxidant (DPPH, FRAP, ORAC) and anti-inflammatory assays. Our results showed that raw Guiana presented equivalent DPPH and FRAP activities, but a 1.3-fold higher antioxidant activity (1097 ± 111.8 μM ET/g DM) than Forastero (838.5 ± 67.8 μM ET/g DM) in ORAC assay. Furthermore, the impact of fermentation (under four conditions: unfermented, two days, four days and six days of fermentation) on Guiana cocoa beans composition and health properties was also studied. Indeed, fermentation, a key step necessary to obtain the taste and color of chocolate, is generally known to alter bean composition and modulate its health benefits. At six days, the fermentation process led to a nearly 25% lower antioxidative capacity in various assays. Moreover, in inflammation-induced macrophage assays, Guiana and Forastero unfermented extracts induced a 112% stimulation in TNF-α production, and a 56.8% inhibition of IL-6 production. Fermentation altered the cocoa composition by diminishing bioactive compounds, which could be responsible for these biological activities. Indeed, after six days of fermentation, compounds decreased from 614.1 ± 39.3 to 332.3 ± 29 mg/100 g DM for epicatechin, from 254.1 ± 14.8 to 129.5 ± 20.7 mg/100 g DM for procyanidin B2 and from 178.4 ± 23.5 to 81.7 ± 2.9 mg/100 g DM for procyanidin C1. The similar composition and the equivalent or higher antioxidant activity of Guiana leads us to propose it as an alternative to Forastero. [ABSTRACT FROM AUTHOR]