Objectives: This study aimed to compare the chemical profile and the anti-oxidant activity of the aqueous methanol extracts (AME) of both Eugenia uniflora L. (EU) and Eugenia supraaxillaris Spring ex Mart. (ES) leaves cultivated in Egypt for the first time. Methods: HPLC/ESI-MS/MS analysis for the AME of both Eugenia species were used to tentatively identify the phenolic compounds. The antioxidant activity was evaluated using DPPH and NO radical scavenging assay. Results: HPLC/ESI-MS/MS analysis for the AME led to the tentative identification of fourteen and twelve compounds in Eugenia uniflora and Eugenia supraaxillaris, respectively. Bioactivity screening showed that the methanolic extract of E. supraaxillaris (IC50 = 8.51±0.37, 14.81±0.63 µg/mL) exhibited stronger antioxidant activity than that of E. uniflora (IC50 = 13.88±0.59, 32.53±1.75µg/mL) through their ability to inhibit DPPH and NO respectively. Also, we found that E. supraaxillaris (IC50 = 8.51±0.37, 14.81±0.63 µg/mL) exerted higher DPPH and NO scavenging activity than that of ascorbic acid (IC50 = 10.21±0.77, 17.95±2.24 µg/mL), respectively, with total anti-oxidant capacity (58.12±2.36 µg/mL) for E. supraaxillaris higher than that of E. uniflora (49.27±1.89 µg/mL) in comparison to the ascorbic acid as a control (69.75±3.81 µg/mL). Conclusion: Our study supports the usage of the AME of both Eugenia species, being efficient antioxidants, in the treatment of serious disorders such as aging, cancer, ischemia and rheumatoid arthritis.