The purpose of this study was to extract, identify, and quantify the phenolic compounds in grumixama (Eugenia brasiliensesLam.) and guabiju (Myrcianthes pungens), native fruits from southern region of Brazil, and to explore their antioxidant and anti-inflammatory properties. The phenolic compounds were extracted with acidified water and acidified methanol and evaluated for their bioactive constituents, antioxidant capacity, and anti-inflammatory properties. Spectrophotometric quantification shows tannins to be the most prevalent at 2.3 to 5.8 g/100g fresh fruit with acidified methanol containing higher concentrations of different phenolics than acidified water. HPLC analysis indicates that gallic acid, catechin, vanillic acid, and ellagic acid are the most prevalent phenolics in the two fruits extracts. Scavenging of DPPH and NO radicals showed inhibition by as much as 95% and 80%, respectively, at 2.5 gallic acid equivalent (GAE)/mL of the extract. At 50 μg GAE/mL, the release of pro-inflammatory molecules NO and IL-6 was significantly reduced with acidified methanol extract having higher inhibitory activity. Our results revealed that these native fruits, grown in the south of Brazil, are rich sources of phenolic compounds and have great antioxidant and anti-inflammatory activity.