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Lipid and protein oxidation are the major causes of meat quality deterioration. Edible mushrooms have been proposed as a strategy to prevent quality deterioration during cold storage. This study aimed to assess the effects of Pleurotus ostreatus powder (POP) on the oxidative stability of pork patties during cold storage and after in vitro gastrointestinal digestion (ivGD). Pork patties were subjected to four treatments: control (without antioxidant), T1 (2% POP, w/w) and T2 (5% POP, w/w), and T3 as positive control (0.02% BHT, fat basis). POP aqueous, ethanolic, and aqueous ethanol extract were subjected to phytochemical and antioxidant assays. Raw pork patties were subjected to a chemical proximate composition evaluation. At the same time, raw and cooked pork patties were stored at 2 °C for 9 days and subjected to meat quality measurements. Furthermore, the total antioxidant activity of cooked pork patties was determined after ivGD. Results showed that POP ethanol extract showed the highest polysaccharide, phenol, and flavonoid content, as well as antiradical and reducing power properties. POP incorporation into raw and cooked pork patties enhances meat quality traits, including pH, water-holding capacity, cooking-loss weight, texture, color, lipid, and protein oxidation (p < 0.05). Furthermore, incorporating POP into cooked samples increases the phytochemical content and antioxidant activity during ivGD. In conclusion, POP has great potential as a natural antioxidant for meat products.