The study of interactions of extracellular membrane-active peptides with host cell membranes is of long-standing interest for both the biological understanding of mechanisms of host-pathogen interactions and their potential for new therapeutics. Exploring the discovery of new classes of membrane active peptides -- capable of lysing or disrupting viral or microbial envelopes -- are of particular importance in the treatment of ongoing infectious diseases. In this vein, [alpha]-helical (AH) peptides -- derived from the hepatitis C virus nonstructural protein NS5A -- are investigated for their potential for a remarkably broad-spectrum virocidal activity. Crucial aspects of their membrane interactions, which determine their biological function and virocidal activity, are however, poorly understood. In this dissertation, I have investigated membrane-peptide interactions using model systems: electroformed Giant Unilamellar Vesicles (GUVs) and supported lipid bilayers deposited on glass. In these model membranes, the AH peptide is shown to discriminate between membrane compositions: In cholesterol-containing membranes, peptide binding induces micro-domain formation and affects permeabilization. By contrast, membranes devoid of cholesterol undergo global softening but only at elevated peptide concentrations. Supported lipid bilayers, also devoid of cholesterol, show arrested diffusion after incorporation. Furthermore, in mixed populations, ~100-nanometer vesicles, which mimic viral dimensions, outcompete the microscopic ones for AH association suggesting curvature-dependent membrane association. These synergistic -- composition- and curvature-dependent --interactions offer insights into how membrane's compositional degrees of freedom couple with peptide binding and explain, in part, how nonstructural proteins might segregate molecules needed for viral assembly at cytoplasmic membranes and provide peptides exhibiting broad-spectrum virocidal activity.