Pomegranate (Punica granatum L.) peel, a byproduct of juice extraction, is rich in phenolics, flavonoids, and tannins, which have bioactive potential. This study aimed to optimize the extraction of bioactive compounds from pomegranate peel extract (PPE). In addition, evaluate its efficacy in inhibiting lipid peroxidation. Total phenolic content (TPC) and DPPH scavenging activity (DPPH•-SA) were used as indicators of antioxidant potential. TPC is widely used as an indicator of antioxidant potential. Phenolic compounds in PPE play key roles in neutralizing free radicals. Extraction was optimized using Response Surface Methodology (RSM) with a Box–Behnken Design (BBD). The effects of temperature, time, and ethanol concentration were assessed. The optimal conditions were identified at 65°C, 60 min, and 70% ethanol. Based on the BBD and statistical analysis using ANOVA, the highest TPC yield was 231.8 mg GAE/g dry weight. The DPPH•-SA of was 92.46%, IC₅₀ of 16.92 µg/mL (95% confidence interval of X-Y µg/mL). The antioxidant performance of PPE was validated in a high-unsaturated lipid system using the Rancimat assay. PPE at 250 µg/g extended the induction period of sunflower oil from 8.32 to 15.90 h. This resulted in a Relative Stability Index (RSI) of 1.91 and a Free Radical Scavenging (FRS%) of 91.11%. These findings demonstrate PPE's potent antioxidant activity, comparable to or exceeding that of synthetic antioxidants like BHT and TBHQ. In conclusion, optimized extraction significantly enhanced PPE's bioactivity, making it a sustainable alternative to synthetic antioxidants in food and healthcare applications.

Pomegranate Peel, Agro-industrial Waste Valorization, Polyphenol Intensification, Box–Behnken Design (BBD) Optimization, Food Preservation, Sustainable Biotechnology