The synthetically evolved pH-dependent delivery (pHD) peptides are a unique family that bind to membranes, fold into α-helices, and form macromolecule-sized pores at low concentration at pH < 6. These peptides have potential applications in drug delivery and tumor targeting. Here, we show how pHD peptide activity can be modulated without changing the amino acid sequence. We increased the hydrophobicity of a representative peptide, pHD108 (GIGEVLHELAEGLPELQEWIHAAQQLGC-amide), by coupling hydrophobic acyl groups of 6-16 carbons and by forming dimers. Unlike the parent peptide, almost all variants showed activity at pH 7. This was due to strong partitioning into phosphatidylcholine vesicle bilayers and induced helix formation. The dimer maintained some pH sensitivity while being the most active peptide studied in this work, with macromolecular poration occurring at 1:2000 peptide:lipid at pH 5. These results confirm that membrane binding, rather than pH, is the determining factor in activity, while also showing that acylation and dimerization are viable methods to modulate pHD108 activity. We propose a possible toroidal pore architecture with peptides in a parallel or mixed parallel/antiparallel orientation without strong electrostatic interactions between peptides in the pore as evidenced by a lack of dependence of activity on either pH or salt concentration.