This article presents a laboratory study of the ozonation of diluted cherry stillage, a high-strength wastewater. Influence of variables, kinetics, and the effects of an ozonation stage coupled with the biological treatment by activated sludge are addressed. Single activated sludge processing was shown effective to remove biological oxygen demand (BOD) and chemical oxygen demand (COD) but polyphenols were reduced to a lesser extent. On the other hand, direct wastewater ozonation did not reduce COD and total organic carbon (TOC) appreciably, and foaming problems were experienced when a high gas flow rate was applied. However, polyphenols and UV254 absorbance decreased substantially by means of ozonation. To best achieve complete cherry stillage purification, two ways of coupling ozonation with activated sludge are proposed. Ozonation prior to activated sludge is advised for high-concentration wastewater to reduce polyphenol concentration, thus removing inhibiting effects. For wastewater with low polyphenol concentration the sequence activated sludge-ozonation-activated sludge is preferred to enhance the overall process performance in terms of oxidation efficiency and sludge settling.