<p>Therapeutic proteins and peptides hold great potential in treating metabolic disorders, infectious diseases, and cancers; however, their oral administration remains challenging due to enzymatic degradation and poor intestinal permeability. To address these limitations, microneedles have emerged as a promising, minimally invasive delivery system to enhance oral bioavailability. This review explores the advantages of microneedles in overcoming physiological barriers to protein and peptide delivery, discussing various types, including solid, dissolvable, coated, hollow, and hydrogel-forming microneedles, in terms of their structural properties, mechanisms of action, and drug release kinetics. Additionally, we examine how microneedles enable controlled and efficient therapeutic protein and peptide release, improving bioavailability and efficacy. Recent research on microneedle applications for transdermal and oral delivery is summarized, alongside a detailed overview of mathematical modeling approaches used to optimize drug release. Microneedles show promise for administering protein and peptides such as vaccines, insulin, and other biologics via the oral route, addressing current limitations in biopharmaceutical delivery. Recent <i>in vivo</i> studies reinforce their feasibility and clinical relevance, demonstrating improved patient compliance and therapeutic outcomes. By offering a safe, effective, and patient-friendly solution, microneedle technology represents a transformative approach to drug delivery, paving the way for non-invasive and convenient therapeutic strategies for protein and peptide-based treatments.</p> Graphical Abstract <p></p>