Pomegranate peel powder (PP), a by-product of the pomegranate juice industry rich in polyphenols, was explored for use in bread production, due to its potential health effects. Wheat bread was prepared using different levels for replacement of flour with PP (0 to 10 g per 100 g flour) resulting in antioxidant levels expressed as Trolox equivalent antioxidant capacity values (TEAC) ranging from 1.8 to 6.8 mu mol TEAC per g bread for fresh bread. TEAC remained constant during 5 days of storage in polyethylene bags at room temperature. The oxidative stability was evaluated by detection of radicals by direct electron spin resonance (ESR) spectroscopy, and peroxide value, and the highest capacity of scavenging of radicals (Fremy's salt) and the lowest content of peroxide values were found in bread with the highest percentage of PP. Safety evaluation was performed by the Artemia salina assay. An increased death rate of the brine shrimp larvae was found as a function of the replacement of wheat flour with PP in fortified bread providing a general screening method for the toxicological test of polyphenol fortified bread to be recommended for use in product development in addition to subjective evaluation. Based on both toxicological and subjective evaluations an addition of 2.5% PP is recommended for the actual product.