The genus Quercus (Fagaceae) is one of the most widely distributed and species-diverse trees in the Northern Hemisphere. The present study addresses the investigation of the phyto-chemical profile by ten assays, the antioxidant activity scavenging of DPPH radicals, total phenolic content, total flavonoids, and antimicrobial activity against three pathogenic bacteria with the foliage of two species of red oak (Quercus sartorii and Quercus rysophylla). Both species of oak showed a high phenolic content in the aqueous extract (22,342.10 ± 3076.5 mg GAE/kg of plant and 17,747.14 ± 1139.9 mg GAE/kg of plant, respectively). In the flavonoid content, Q. sartorii showed a higher amount in the ethanolic extract (24,587.42 ± 996.3 mg QE/kg of plant), while for Q. rysophylla, it was methanolic extract (19,875.66 ± 2754.01 QE/kg of plant). In the DPPH radical scavenging activity, Q. sartorii showed the highest percentage of inhibition in the methanolic extract (81.14 ± 1.7%), while in Q. rysophylla, it was the ethanolic extract (82.60 ± 2.7%). In the antimicrobial tests, inhibition halos were obtained in the strains Acinetobacter baumannii and Staphylococcus aureus of both species. All this gives a guideline to comprehensively elucidate the metabolites present in these two species for further study and application in the dispute against pathogenic bacteria or in diseases related to the imbalance of reactive oxygen species (ROS).