Background: Moringa oleifera is a tree that grows in tropical and subtropical areas around the world. Its leaves, seeds, bark, roots, and flowers are used as ingredients in meals and medicinal applications. Moringa leaf extracts have been studied to contain antioxidant compounds such as phenolic molecules. Recent extraction techniques such as ultrasound and microwaves are alternatives to increase the extraction performance of phenolic compounds while preserving their antioxidant activity.Objective: The approach consisted of optimizing, using a Composite Central Design of Response Surface Methodology (CCD-RMS), the process conditions, for ultrasound-assisted extraction (UAE) of antioxidant phenolic compounds from Moringa oleifera leaves. Methods: A 33 CCD-RMS was used; three independent variables were studied: ethanol concentration (25%, 50%, 75%), time (10, 20, and 30 min), and temperature (25, 37.5, and 50°C). The results showed that the optimal UAE conditions were an ethanol concentration of 52.4%, extraction time of 3.2 min, and temperature of 58.5°C; under these conditions the phenolic content was 13.92±0.21 mg GAE/g sample the total flavonoid content was 10.60±0.06 mg QE/g sample, and 52.22±2.01% and 72.81±1.58% of DPPH• and ABTS•+ radicals were inhibited, respectively.Conclusion: This optimization will make it possible to assess better use of M. oleifera leaves as an antioxidant ingredient in functional food development.Keywords: Moringa oleifera, composite central design, optimization, flavonoids, phenols, antioxidant activity.