BACKGROUND: Natural antioxidants have received increased attention owing to their safe use without side effects; however, their application has been limited because of lower antioxidant activity and stability during digestion when compared with those of synthetic antioxidants. Although research is ongoing to overcome these problems, it is still challenging to find effective solutions. In this study, we aimed to improve the properties and stability of natural antioxidants during in vitro digestion by synergistic combination and nanoencapsulation. RESULTS: Ten selected fruit and vegetable concentrates (acai berry, aronia, blackberry, cranberry, wild berry, raspberry, blueberry, red grape, cabbage, and spinach) were evaluated for their antioxidant capacity when combined via the oxygen radical absorbance capacity (ORAC) assay. Among the 45 combinations, the highest synergistic ORAC value was noted for the blueberry and cabbage concentrates (BUCA; 0.8 and 1.2 mg mL −1 ) at an antioxidant ratio of 5:5. Chitosan/carrageenan (CSCR) nanoparticles are physically more stable than chitosan/gum arabic nanoparticles during in vitro digestion and were selected for the oral delivery of BUCA. Under simulated intestinal conditions, BUCA-loaded CSCR nanoparticles showed significantly more stable antioxidant activity and total phenolic content than non-nanoencapsulated BUCA. The highest antioxidant stability was observed in the BUCA-loaded CSCR nanoparticles prepared with 0.2 mg mL −1 carrageenan, which showed two-times higher ORAC value and ten-times higher total phenolic content than non-nanoencapsulated BUCA after 12 h of in vitro digestion. CONCLUSION: CSCR nanoencapsulation of natural antioxidants could be an effective technique for improving antioxidant stability during digestion. Determination of entrapment efficiencyThe entrapment efficiency (EE) of the nanoparticles was indirectly evaluated using an Amicon Ultra-4 centrifugal filter device, which excludes everything larger than a 3000 nominal molecular weight limit. The nanodispersion (2.0 mL) was centrifuged at 7000 × g for 35 min using an Amicon Ultra-4 centrifugal filter device, and the total phenolic contents of the filtrate-excluded nanoparticles were