Peptides represent a rapidly expanding class of drugs with broad therapeutic potential. However, due to their large molecular weight and susceptibility to degradation in the gastrointestinal tract, most peptide drugs are administered via subcutaneous injections. Despite extensive research, a painless broad delivery platform for these drugs is still lacking. Recently, an octopus-inspired buccal patch has shown promise in addressing this challenge by leveraging a synergistic combination of mechanical stretching and permeation enhancers. In this study, the patch and the loaded formulation were optimized to improve ease of use, scalability, and efficacy. Through assessments of mechanical properties, finite element simulations, and ex vivo experiments, we evaluated the effects of patch design and material, as well as the drug matrix composition and the formulation preparation methods on the delivery performance. A patch with a > 9-fold larger effective surface area, produced via mold casting of medical-grade silicone (shore hardness 50) and loaded with a lyophilized drug matrix, emerged as the most promising system. In beagle dogs, 30-min application of this patch resulted in a 14.6 % bioavailability for teriparatide (4118 g mol), while bioavailability of semaglutide (4114 g mol) was 9.6 times higher than that of the commercial tablet. This work showcases how systematic optimization of this technology can improve and simplify the buccal administration of macromolecular drugs, facilitating the clinical translation of this non-invasive dosage form.