The peel of pomegranate fruit contains antioxidant phytochemicals that may potentiate health benefits but remain under-explored. We evaluated the antioxidant, nutritional and phytochemical profiles of the peel of the "Wonderful" variety pomegranate and its influence on oxidative metabolic alterations in hepatic tissue. The peel contained appreciable amounts of some beneficial trace minerals and both essential and non-essential amino acids. Mostly Omega 3 and 6 fatty acids were found. The peel extracts exhibited in vitro radical scavenging and Fe 3+ reducing antioxidant activities and dose-dependently prevented oxidative stress-induced lipid peroxidation increase and GSH depletion in both Chang liver cells (IC 50 = 18.0 ± 1.46 and 11.2 ± 0.99 µg/ mL, respectively) and isolated rat liver (IC 50 = 96.7 ± 3.34 and 19.4 ± 3.36 µg/mL, respectively). The antioxidant effects were comparable to that of ascorbic and correlated with their phenolic profile. HPLC analysis further identified antioxidant phenolic acids (gallic acid, syringic acid ferulic acid p-coumaric acid or trans-4-hydroxycinnamic acid, etc.). The peel did not cause notable cytotoxicity in liver and kidney cells, which suggest minimal safety concerns. Metabolomics analysis revealed alterations in fatty acid, amino acids, and nucleic acid metabolisms following the induction of oxidative stress. These alterations were improved in the acetone extract-treated tissues, with concomitant activation of vitamin and selonocompound metabolisms. Data suggest that the fruit peel of "Wonderful" pomegranate may be an underutilized source of functional nutrients and antioxidants phenolic acids for optimum body function and mitigation hepatic oxidative damage and metabolic alterations as well as associated diseases.

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