In recent years, there has been a significant increase in the chestnut processing industry, leading to the generation of substantial amounts of by-products that are causing disposal challenges and environmental consequences within the post-harvest supply chain of Castanea spp. nuts. In particular, chestnut episperm, produced in large quantities during post-harvest processing, shows potential to serve as a valuable source for extracting antioxidant compounds, including phenolics. This study has developed an environmentally sustainable method for extracting the polyphenols and antioxidants with best health-promoting properties from chestnut episperm (cv Marsol, C. sativa × C. crenata) using ultrasound technology. High-performance liquid chromatography (HPLC) was used to assess the levels of specific phenolic compounds known for their health benefits and antioxidant capacity. The total polyphenolic content (TPC) ranged from 90 to 150 mg GAE/g of dried weight (DW). Furthermore, a Ferric Reducing Antioxidant Power (FRAP) assay confirmed the high TPC levels in the extract, showing that all the extracts presented high levels of antioxidant properties (approximately 470–515 mmol Fe²⁺/Kg of dried weight for the most effective extracts). The proposed method enabled the production of preparations containing significant amounts of castalagin (20–80 mg/100 g DW), chlorogenic acid (15–25 mg/100 g DW), vescalagin (40–75 mg/100 g), and ferulic acid (80–120 mg/100 g DW). This investigation demonstrated the potential of chestnut episperm as an innovative source of antioxidants, which may be extracted using sustainable technologies and utilized in industry applications as pharmaceutical and/or food products, thereby promoting the valorization of agri-food waste through a low-impact reuse strategy and reducing environmental impacts. Chestnut companies stand to benefit financially by extracting antioxidant molecules through processing post-harvest wastes like episperm and marketing these preparations, thereby avoiding expenses associated with by-product disposal and potentially increasing their incomes.