Abstract: Background and Objective: Nanoencapsulation involves coating for bioactive compounds and can strongly affect their mechanical, formative properties, bioavailability and stability. The aim of this study was to benefit the bioactive compounds extracted from Egyptian prickly pear peel fruit in nanoencapsulation formula to protect and improve their stability and bioavailability and evaluate their activity comparing to synthetic ones. Materials and Methods: Bioactive compounds were extracted by ethanol, exposed to ultrasonic water bath, then encapsulated in two natural polymers (sodium alginate and chitosan) using nanotechnology techniques aside with their chemical and physical evaluation and application in guava juice. Results: No significant differences in DPPH radical-scavenging activity were observed between ethanol extract (EE) and nanoencapsulate formulas (NEE-Chi and NEE-Algi+Chi) of prickly pears peels fruit extract at 15 mg mL–1 concentration. While, scavenging activity of prickly pears peels fruit extract in NEE-Alg at the same concentration was also significantly less than other formulas. Nanoencapsulate extract in chitosan (NEE-Chi) and NEE-Alg+Chi formulas had the highest reducing power activity (481.76 and 462.49 μg GAE/100 g DW), respectively. The highest nanoencapsulated yield and efficiency were observed for NEE-Chi formula being 91.74 and 97.81%, respectively. Thermal stability (DSC) of nano-encapsulated increased after nano-encapsulation showing the highest results with NEE-Alg+Chi being 219.53°C. The addition of NEE-Alg+Chi to guava juice showed significantly affected the taste, odor, color, mouth feel, appearance and overall acceptability being 6.9, 6.7, 6.8, 6.8, 6.8 and 6.7, respectively, compared to other samples of guava juice supplemented with prickly pears peel fruit extracts. The highest content of total antioxidant capacity in guava juice samples was found in NEE-Chi formula stored for 120 days at 23°C. Conclusion: The impact of this study indicated that nanoencapsulation affects positively the bioactive compounds extracted from prickly pears peels fruit, improves the antioxidant activity, enhancing the quality and stability of bioactive compounds.