Peptide dendrimers have unusual multi-branched architectures with cell-penetrating properties. They have found applications as intracellular delivery agents for cell-impermeable drugs. The aim of this study is to investigate dendrimeric cores of different physical properties and its impact on penetration. Using Fmoc-based solid-phase peptide synthesis, we successfully synthesized five Lys-based dendrimers with varied physical properties. Through mass spectrometry-based artificial lipid permeability assays, we found that alanine core dendrimers exhibit lipid permeable capabilities. In conclusion, hydrophobic dendrimeric cores enhance lipid permeability which is crucial for direct cell penetration.