The blueberry fruit of the genus Vaccinium, including high blueberry, low blueberry, and wild bilberry, is consumed for its flavor and medicinal properties. The purpose of the experiments was to investigate the protective effect and mechanism of the interaction of blueberry fruit polyphenol extracts with the erythrocytes and their membranes. The content of polyphenolic compounds in the extracts was determined using the chromatographic UPLC–ESI–MS method. The effects of the extracts on red blood cell shape changes, hemolysis and osmotic resistance were examined. Changes in the order of packing and fluidity of the erythrocyte membrane and the lipid membrane model caused by the extracts were identified using fluorimetric methods. Erythrocyte membrane oxidation was induced by two agents: AAPH compound and UVC radiation. The results show that the tested extracts are a rich source of low molecular weight polyphenols that bind to the polar groups of the erythrocyte membrane, changing the properties of its hydrophilic area. However, they practically do not penetrate the hydrophobic part of the membrane and do not damage its structure. Research results suggest that the components of the extracts can defend the organism against oxidative stress if they are delivered to the organism in the form of dietary supplements.