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Medium-chain fatty acid-based permeation enhancers (PEs) have gained significant attention due to their potential application in various industries, including within the pharmaceutics sector as absorption enhancers for, e.g., peptide drugs. In this study, we performed computational experiments to investigate the impact of two different PEs, capric acid and Salcaprozate sodium (SNAC), at three different concentrations (0%, 30%, 50%), on the structural properties of a bilayer consisting of 70% 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 30% cholesterol. We employed coarse-grained molecular dynamics simulations first to explore the interactions of the PEs with lipid bilayers at the molecular level and then to examine the consequences of these interactions for the permeability of three different peptides (octreotide, desmopressin, and triptorelin). We employed umbrella sampling simulations to obtain the permeability rates of the PEs at several concentrations and of the peptides in the absence and presence of the two PEs, also at different concentrations. We observed that the impact on the membrane structural properties changed with increasing PE concentration. We also found that the effective permeability values increased with increasing PE concentration. However, the permeability values were significantly higher (6-7 orders of magnitude) for capric acid than for SNAC, which we argue is mainly because capric acid has more pronounced effects on the structural properties of the membrane. Peptide permeability also increased with increasing PE concentration. The Peff values followed the trend: octreotide > triptorelin > desmopressin across all systems. For each peptide, the lowest Peff values were observed in the no-PE systems, while the highest values were observed in the systems with 50% capric acid. Capric acid exhibited an increasing trend in Peff values with higher concentrations within the membrane. In contrast, the peptide Peff values in the SNAC systems were similar between the 30% and 50% concentrations, aligning with the trends observed in free energy profiles and the membrane structural characteristics. Thus, for SNAC, there seems to be a concentration where the permeability-enhancing effect plateaus. With these results, we hope to pave the way for more knowledge-based design of pharmaceutical dosage forms that involve PEs for increasing transcellular peptide permeability, considering the differences in compatibility between PEs and peptides, and the apparent synergistic effect of combining PEs.