First, in the water layer, SNAC associates with semaglutide, acting as a surfactant to help monomerize the peptide while remaining partially deprotonated. Second, upon membrane insertion, SNAC neutralizes and forms dynamic, hydrogen bond-driven membrane defects to help facilitate membrane permeation of the peptide drug. Our proposed mechanism for the passive membrane permeation of semaglutide is unprecedented, being the first to be substantiated by accurate CpHMD atomistic models (with all weakly ionizable functional groups in both the peptide and all the permeation enhancers modeled with CpHMD). While it delineates one of numerous potential pathways for semaglutide to traverse a membrane in the presence of SNAC, the integration of scalable CpHMD elevates it to one of the most expansive and accurate models documented to date. Moreover, the overarching principles elucidated in this study -specifically, SNAC's behavior in nonpolar environments, its dynamic aggregation with semaglutide in both polar and nonpolar contexts, and the formation of SNAC-filled dynamic defects within the membrane -present foundational concepts, which hold significant potential to inform and refine the development of novel peptide drug/permeation enhancer combinations in the future. The adhesion of semaglutide to the membrane, which was observed in our CpHMD simulations, also agrees with the initial steps for cell translocation of known cell-penetrating peptides. Overall, our results provide a new viable mechanism for cell permeation to help advance the field of oral peptide drug delivery, including potentially for macrocyclic peptides in the future.