SummaryPomegranate‐peel polyphenols, specifically the punicalagin, have gained importance due to their potential antioxidant capacity, and because of this have been proposed different methodologies to encapsulate and protect the polyphenols for proposing their uses. The objective of the present work was to optimize the spray‐drying of pomegranate‐peel polyphenols and additionally to evaluate their antioxidant activity based on lipid oxidation inhibition. The spray‐drying process was optimized via Taguchi L9 orthogonal array considering the feed flow (3.0, 4.5, and 6.0 mL/min), temperature (125, 150, and 200 °C), and airflow (30, 35, and 40 m3/h). The lipid oxidation inhibition was the response variable. The optimal spray‐drying conditions were experimentally validated, and the changes in polyphenols were analysed by HPLC‐ESI‐MS. The spray‐drying conditions optimized at which the polyphenols better preserved their antioxidant capacity (i.e., 87.40 % of inhibition) were feed flow, 4.5 mL/min; temperature, 125 °C; and airflow, 35 m3/h. However, temperature control was the most critical factor for obtaining good quality spray‐dried polyphenols (37.65 % of influence). This permitted us to propose that spray‐dried pomegranate‐peel polyphenols could be used as antioxidants in edible oils.