Ethnopharmacological relevance: The investigation of Brazil's vast plant biodiversity is crucial. The genus Pouteria, though minimally explored chemically and pharmacologically, has numerous ethnopharmacological reports. Aim of the study: This study aims to evaluate the antioxidant, anti-inflammatory, antinociceptive, angiogenic, and cytotoxic properties of hydroethanolic extract from the leaves of P. guianensis, as well as to characterize its chemical composition. Material and methods: Several extracts from P. guianensis leaves were evaluated for antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) reduction model. Chromatographic analyses and chemometric correlations were also applied. The 80 % hydroethanolic extract was selected and dereplicated using spectrometric techniques, and its anti-inflammatory and antinociceptive activities were assessed through carrageenan-induced paw edema, pain models, and the hot plate test. Antiangiogenic properties were evaluated using the chorioallantoic membrane (CAM) technique and cytokines levels were also measured. Results: Chemometric analyses identified myricitrin as a potential active marker for antioxidant activity, with mass spectrometry revealing a high phenolic content, particularly flavonoids quantified at 2.47 % and tannins at 17.19 %. Previous oral administration (p.o.) of the 80 % hydroethanolic extract of P. guianensis demonstrated significant anti-inflammatory and antinociceptive effects without impairing the animals’ motor function. The hydroethanolic extract reduced TNF-α and IL-1β levels and also exhibited antiangiogenic properties, suggesting potential mechanisms for its anti-inflammatory action. Furthermore, no toxicity was observed in the CAM model. Conclusion: This study highlights the significant pharmacological activities of P. guianensis hydroethanolic extract, warranting further investigation into its mechanisms of action. Additionally, it provides the first chemical characterization of the species, revealing a high phenolic content.