Pyrus communis (P. communis) is the most cultivated and consumed species of pear within the European continent. This fruit has been a staple in Greece since ancient times, hence the name “Gift of the Gods”. Given the extensive utilization of this fruit in the industrial sector and the focus on the exploitation of by-products to create new food and beverage products, the present research aimed to enhance the antioxidant activity of the P. communis peel through the implementation of a multifactor extraction system. Increased total polyphenols and ascorbic acid concentration, and enhanced antioxidant activity through radical scavenging and Fe3⁺ to Fe2⁺ reduction, all assist in boosting the health benefits of the extracts. The results indicated that the best conditions for compound yields were a 75% v/v hydroethanolic concentration, an extraction temperature of 80 °C, and 30 min of extraction time. Under the optimal conditions, the total polyphenol content was up to 4.98 mg of gallic acid equivalents (GAE)/g dried weight (dw). The radical scavenging activity by the 2,2-diphenyl-1-picrylhydrazyl (DPPH•) method was expressed as 18.36 μmol ascorbic acid equivalents (AAE)/g dw, while by the ferric-reducing antioxidant power (FRAP) method, it was 35.09 μmol AAE/g dw. Finally, the amount of ascorbic acid was measured at 20.16 mg/100 g dw. In this regard, this study has been conducted to assess and enhance the level of these bioactive compounds in the extract of the P. communis peel, leading to an extract with several applications in different food and beverage industries.