Alzheimer's disease is a devastating pathology affecting an increasing number of individuals following the general rise in life expectancy. Amyloid peptide Aβ_1–42 has been identified as one of the main culprits of the disease. The peptide has been shown to have major effects on lipid membranes, including membrane fragmentation. The membrane composition has been identified as a factor that plays a pivotal role in regulating peptide/membrane interactions and several results suggest that lipid domains, or rafts, can promote peptide-induced membrane damage. In this work, we examined the effects of lipid segregation on the membrane-perturbing ability of Aβ_1–42 and an oligomeric mutant (G37C), a peptide that shares common features with the suspected toxic intermediates involved in the neurodegeneration process. Atomic force microscopy (AFM) was used to determine the impact of these peptides on the supported lipid bilayers of various compositions. In 1,2-dioleoyl-sn-glycero-3-phosphocholine/1,2-dipalmitoyl-sn-glycero-3-phosphocholine/cholesterol (DOPC/DPPC/cholesterol) and DOPC/sphingomyelin/cholesterol ternary mixtures, two systems exhibiting liquid–liquid phase separations, it was shown that Aβ_1–42 and G37C exclusively aggregated on liquid-disordered-phase domains, creating large deposits and even causing membrane fragmentation for the latter composition. Cholesterol and ganglioside GM1, the two most documented lipids in the context of Alzheimer's disease, are also considered to play a crucial role in promoting detrimental interactions with amyloid peptides. We show that, in model 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes, the presence of either cholesterol or GM1 in a proportion of 10 mol%, a content supposed to lead to domain formation, favoured the association of both Aβ_1–42 and G37C, leading to a harmful membrane fragmentation. The AFM results established that the presence of domains favoured membrane perturbations induced by the amyloid peptides. It is proposed that lipid packing defects at the domain interface could act as adsorption and nucleation sites for the amyloid peptides. The more extensive bilayer perturbations induced by G37C compared to Aβ_1–42 supported this hypothesis, indicating that oligomers that cannot mature to the fibril state can present considerable toxicity.