Many years ago, β 2/β 3‐peptides, consisting of alternatively arranged β 2‐ and β 3h‐amino‐acid residues, have been found to undergo folding to a unique type of helix, the 10/12‐helix, and to exhibit non‐polar, lipophilic properties (Helv. Chim. Acta 1997, 80, 2033). We have now synthesized such ‘mixed’ hexa‐, nona‐, dodeca‐, and octadecapeptides, consisting of Val‐Ala‐Leu triads, with N‐terminal fluorescein (FAM) labels, i.e., 1–4, and studied their interactions with POPC (=1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine) giant unilamellar vesicles (GUVs) and with human white blood cancer cells U937. The methods used were microfluidic technology, fluorescence correlation spectroscopy (FCS), a flow‐cytometry assay, a membrane‐toxicity assay with the dehydrogenase G6PDH as enzymatic reporter, and visual microscopy observations. All β 3/β 2‐peptide derivatives penetrate the GUVs and/or the cells. As shown with the isomeric β 3/β 2‐, β 3‐, and β 2‐nonamers, 2, 5, and 6, respectively, the derivatives 5 and 6 consisting exclusively of β 3‐ or β 2‐amino‐acid residues, respectively, interact neither with the vesicles nor with the cells. Depending on the method of investigation and on the pretreatment of the cells, the β 3/β 2‐nonamer and/or the β 3/β 2‐dodecamer derivative, 2 and/or 3, respectively, cause a surprising disintegration or lysis of the GUVs and cells, comparable with the action of tensides, viral fusion peptides, and host‐defense antimicrobial peptides. Possible sources of the chain‐length‐dependent destructive potential of the β 3/β 2‐nona‐ and β 3/β 2‐dodecapeptide derivatives, and a possible relationship with the phosphate‐to‐phosphate and hydrocarbon thicknesses of GUVs, and eukaryotic cells are discussed. Further investigations with other types of GUVs and of eukaryotic or prokaryotic cells will be necessary to elucidate the mechanism(s) of interaction of ‘mixed’ β 3/β 2‐peptides with membranes and to evaluate possible biomedical applications.