Changes in the abundance and properties of blood lipoproteins are generally considered major causes for varied pathological conditions and diseases. Using novel chromatic biomimetic vesicle and cell assays, we present here for the first time evidence for significant changes in lipoproteins' interactions with artificial membranes. Specifically, we demonstrate significant differences in membrane binding between lipoproteins (both low-density lipoprotein [LDL] and high-density lipoprotein [HDL]) harvested from diabetic patients vs. healthy controls as well as between oxidized and native lipoproteins. The chromatic assays, complemented by biophysical techniques and electron microscopy, point to significant reduction of surface membrane binding of the lipoproteins as a consequence of diabetes or oxidation. Overall, our results indicate that the substantial modulation of membrane interactions revealed by the chromatic assays may be used as a new and potentially powerful marker for screening and prediction of diseases associated with oxidative stress.