Interactional and structural analyses of lipids in hydrated biomembranes are at the frontier of membrane physics and biology. Recently, solid-state NMR has emerged as a frequently used technique for the investigation of biomembrane systems, leading to particularly remarkable advances in the study of the structural biology of membrane proteins. However, conformational and interactional analyses of lipid molecules and membrane-active small compounds remain challenging. This chapter highlights recent applications of solid-state NMR to membrane lipids and nonpeptidic molecules such as membrane-active natural products. Lipid rafts are microdomains in cellular membranes formed by sphingomyelin and cholesterol and are thought to constitute a platform for signal transduction. Amphotericin B, theonellamide-A, and amphidinol 3 exert their activities by interacting with lipid membranes. Deuterium quadrupole coupling combined with dipole–dipole interactions has been used to evaluate the interaction modes and dynamic properties of membrane lipids and small membrane-active compounds. Herein, we review the recent advances in these topics using our recent research studies as examples of solid-state NMR investigations of hydrated lipid bilayers.