The leaves of blueberry are a rich source of polyphenols, chlorogenic acid (CGA) being the dominant constituent. It exerts beneficial health effects on living organisms. However, the mechanism of its interaction with biological systems at the molecular and cell level is not yet fully known. For this reason, biophysical studies were undertaken to investigate the effect of the polyphenolic compounds contained in the extract on the physical properties of cells, biological and model lipid membranes; and to assess the extract’s antioxidant activity in relation to the erythrocyte membrane and membrane lipids extracted from erythrocyte membranes. The hemolytic studies have shown that extract exert no destructive effect on the erythrocyte membrane, but make it more resistant to changes in tonicity of the medium. The studies of shapes of erythrocytes and of changes induced by the extract in different areas of the membrane showed that the compounds bind mainly to the outer lipid monolayer of the membrane. The biological activity of the polyphenolic compounds present in the blueberry leaf extract consists primarily in protecting the membranes against the harmful effects of free radicals, probably owing to a barrier that they form on the surface of the membrane. In addition, the close link demonstrated between the antioxidant activity of the extract and the activity of CGA means that the extract may, at appropriately selected high concentrations, be used as a widely available, cheap CGA substitute, in those pharmacological preparations where CGA has long been used, without the risk of side effects.