Oral delivery of biopharmaceuticals can be enhanced by some cell-penetrating peptides applied as carriers. The objective here was to improve the permeability enhancing properties of such two peptides by branching into dimer and trimer variants. The transepithelial permeation of cargos including insulin, dextran, mannitol, and metoprolol mediated by penetratin and its analogue penetramax in their linear and branched versions was evaluated in the Caco-2 cell culture model. The enhancing properties of penetramax and particularly penetratin were significantly increased in accordance with the degree of branching, overall increasing the potency of the molecule. The enhanced cargo permeation was associated with peptide-induced effects on the Caco-2 cell monolayers including immediate and reversible decrease in integrity and alterations of the cell cytoskeleton. Overall, the results of the in vitro studies display that the paracellular pathway is involved in the enhanced cargo permeation and that peptide modification by branching indeed increases the permeation of cargos. In vivo pharmacokinetic and histological assessment with insulin as a cargo confirmed the potential of dimeric penetramax as a carrier in comparison to its linear counterpart.