The interaction of membrane proteins with and within lipid membranes is vital to a plethora of cellular processes from the control of intracellular signaling by peripheral membrane proteins, to the activity of antimicrobial peptides and integral membrane proteins. Thus, quantifying the mechanism by which proteins interact with and within lipid membranes is essential to understanding their biological functions. However, many protein-lipid and protein-protein interactions remain poorly understood due to the difficulty in studying processes that occur at the membrane surface. There is thus a clear need for a sensitive, versatile, non-perturbing and physiologically-relevant biophysical method capable of measuring association constant and stability free energy of membrane proteins in a wide range of conditions and matrices.Backscattering interferometry (BSI) is an analytical technique that can monitor and quantify molecular interactions through the detection of small changes in refractive index (RI) induced by molecular interaction. BSI offers many advantages over current techniques including: no need for label or surface immobilization, small sample sizes (1-2 µL), low concentrations (pM to µM), remarkable sensitivity, broad dynamic range for dissociation constant, and low cost. Here, the potential application of BSI in the field of membrane proteins is illustrated through three case studies: (1) Association of small peptides with lipid vesicles, (2) transmembrane helix dimerization, and (3) unfolding of integral membrane proteins. Our preliminary results suggest that BSI is amenable to the study of such systems.