The native cell membrane nanoparticles (NCMN) system utilizes membrane-active polymers specifically designed and optimized to extract and stabilize membrane proteins in the form of NCMN particlesfor biochemical and biophysical characterization. The NCMN system is a genuine and advanced detergent-free approach inspired by the membrane activity of the styrene–maleic acid copolymers (SMA), distinguishing it from the nanodisc technology, Salipro technology, and Peptidisc technology. This review introduces the current advancements in the NCMN system, including the development of NCMN polymers, the application of the NCMN system for single-particle cryo-EM analysis, and the functional characterization of membrane proteins.