This review explores the challenges and strategies in oral delivery of peptide and protein therapeutics. Physiological barriers such as the gastrointestinal tract, enzymatic degradation, poor permeability and proteolytic environment hinder effective delivery. Formulation approaches including bioavailability enhancement, mucoadhesive systems, nanoparticle-based, lipid-based, and polymer-based delivery systems have shown promise in improving solubility, stability, and permeability. Innovative technologies like nanotechnology-based delivery, targeted approaches, drug-device combinations, and bioadhesive/mucoadhesive technologies offer new avenues for overcoming challenges. Strategies to combat enzymatic degradation involve protease inhibitors, enzyme-resistant formulations, chemical modifications, and encapsulation strategies. Enhancing permeability across the intestinal epithelium can be achieved through absorption enhancers, carrier-mediated transport systems, tight junction modulators, and nanotechnology-based approaches. Preclinical and clinical studies provide insights into oral delivery efficacy, safety and patient acceptance. Future directions include advances in delivery, emerging technologies, regulatory considerations and patient compliance. This review offers a comprehensive overview for researchers and clinicians in the field.