<p>Mucoadhesive drug delivery systems have gained significant attention in recent years for both local and systemic drug delivery due to their exceptional approachability, ability to avoid first-pass metabolism, large blood supply, safety, and enhanced patient acceptability. This review comprehensively explores the mechanisms, theories, and factors influencing mucoadhesion, as well as the classification and characterization of mucoadhesive polymers. The two-step process of mucoadhesion involves the contact stage, where the mucoadhesive spreads and initiates deep contact with the mucus layer, and the consolidation stage, where the mucoadhesive materials are activated by moisture, allowing for interpenetration and entanglement of polymer chains with mucin. Various theories, such as wettability, electronic, fracture, adsorption, and diffusion theories, have been proposed to explain the mucoadhesion phenomenon. Factors affecting mucoadhesion include polymer-related properties like molecular weight, flexibility, hydrogen bonding capacity, cross-linking density, charge, concentration, and hydration, as well as environmental and physiological factors such as pH, contact time, swelling, and mucin turnover rate. Mucoadhesive drug delivery systems(DDS) offer several advantages over conventional drug delivery methods due to their ability to adhere to mucosal tissues such as those in the oral cavity, gastrointestinal tract, nasal passages and vaginal or rectal areas and it enhances bioavailability, sustained and controlled drug release, targeted drug delivery, Improved patient compliance, protection against degradation, versatile applications, lower dose requirement compared to conventional drug delivery system. Overall, mucoadhesive drug delivery systems offer a promising approach for enhancing drug bioavailability, prolonging residence time, and improving patient compliance across a wide range of therapeutic applications.</p>