Exploration of the relation between the structural feature of oligomers and the ability of oligomers to damage the membrane has been an important subject in the study of the cyt otoxic mechanism of amyloid proteins. In this work, we selected the hIAPP(18-27) fragment as a model peptide and modified it by an alternating substitution of a D-amino acid for an L-amino acid in the hydrophilic N-terminal region, the hydrophobic C-terminal region, and the entire sequence. We prepared the oligomers using these peptides and investigated the effects of chain extension in different regions of the peptide on the ability of the oligomers to damage the membrane composed of POPC/POPG 4:1. We examined the morphology, structure, surface hydrophobicity, and packing compactness of the oligomers and monitored the changes in the structure and aggregation of the peptides upon interaction with the membrane. We found that the surface hydrophobicity and the disruptive ability of the oligomers are increased by an alternating L- and D-amino acid arrangement in the hydrophobic region of the peptide, while the packing compactness of the oligomers is increased and the disruptive ability of the oligomers decreased by an alternating L- and D-amino acid arrangement only in the hydrophilic region. The extension of the hydrophobic chain plays a significant role in the disruptive ability of the oligomers. Our results suggest that a positive relation between the surface hydrophobicity and the disruptive ability could be established only for the oligomers in which the peptide chains are flexible and loosely packed.