Origanum vulgareis recognized worldwide for its numerous applications, in the food industry and beyond. However, the extraction of its essential oils generates a significant amount of waste. The aim of this research was to achieve the valorization of solid waste from oregano hydro-distillation, by (i) optimizing the ultrasound extraction of antioxidants, (ii) evaluating the effect of spray and freeze drying on the extract’s physicochemical properties, and (iii) characterizing the obtained powder by its antioxidant capacity. A central composite design of experiments was used to optimize the sample/solvent ratio, ethanol/water ratio, and extraction time. The extract was analyzed for its antioxidant potential by determining the percentage of DPPH inhibition, FRAP, and total phenolic content (TPC). The GAB model best fit the data for the moisture sorption isotherm of the resulting powder. The antioxidant activity of the powders was tested in a ground-beef food system. The TPC was maximized at times longer than 58 min, a sample/solvent ratio between 0.058 and 0.078, and a ratio of ethanol/water around 1. Neither drying method significantly affected the antioxidant properties of the extract, even though the resulting powders from each showed a different morphology (determined using SEM). Encapsulation with maltodextrin protected the spray-dried extract during a 6-month storage period. Powders from both drying methods equally retarded lipid oxidation, and were comparable to the synthetic antioxidant BHT. It is concluded that oregano processing waste is a potent source of antioxidants, and that its dried extract, via an ultrasound-assisted process, can potentially be used as a natural alternative to synthetic antioxidants.