Membrane proteins are embedded within the biological membrane and encircled by an annular belt of lipids. Understanding the composition and dynamics of this annular belt is essential for advancing our knowledge of membrane proteins, which play critical roles in various physiological functions of living cells. Native mass spectrometry (MS) allows for the detection of intact membrane protein–lipid complexes in the gas phase. However, the conventional approach of solubilizing membrane proteins in detergents often interferes with the analysis of protein–lipid interactions due to the properties of the chosen detergent. In this study, we demonstrate how charge-reducing detergents and molecules, such as spermine, reduce the overall charge of membrane protein–lipid complexes, enabling the investigation of the annular lipid belt surrounding membrane proteins.