Introduction: Beyond the commercial value of coffee grains there is recent interest for the non-timber benefit and traditional medicinal properties of the Coffea tree leaves.Objective: To determine the phytochemical composition, antioxidant properties and inhibition of oxidative stress by extracts from Coffea leaves obtained by ultrasound assistance as an opportunity for production of plant bioactives. Material and methods: The phytochemical composition of ten extracts of Coffea arabica L. leaves cv. Catimor 5000 was evaluated in their phenolic and methylxanthines contents as well their antioxidant activity in vitro through nitric oxide (NO), absorbance capacity of oxygen radicals (ORAC), ferric reducing antioxidant power (FRAP), and radical ABTS (2,2'-azino-bis [3-ethylbenzothiazoline-6-sulfonic acid]) assays, and their effect on inhibition of oxidative stress induced by hydrogen peroxide in human colon adenocarcinoma cells (HT-29). Extracts were obtained by ultrasound assistance under different conditions (wave amplitude, solvent ratio, and extraction time). Results and discussion: The higher phenolics and caffeine contents, as well the greater oxidative stress inhibition response in the HT-29 model, ORAC and NO assays were obtained at 60/40 water/methanol, 40 % amplitude and 6 min of extraction time. In this work, identification of two flavanones have been reported for the first time in Coffea leaves: neohesperidin and naringenin. Regarding phenolic acids, it was detected and identified a group of hydroxybenzoic acids not previously reported in coffee leaves, such as vanillic, shikimic, syringic, and ellagic acids, along with 2,4,6 trihydroxybenzaldehyde and 2,3 dihydroxybenzoic acid.Conclusion: The novel phytochemical composition of bioactive extracts from Coffee leaves by ultrasound assistance is significant, representing a potential source of food nutraceuticals.