Mucoadhesive drug delivery systems are advanced pharmaceutical formulations designed to interact with the mucus layer covering mucosal epithelial surfaces and prolong the residence time of a dosage form at the site of administration or absorption. These systems utilize interactions between mucoadhesive polymers and mucin glycoproteins present in the mucus layer, thereby enhancing drug retention and improving therapeutic efficacy. Prolonged gastrointestinal (GIT) residence is particularly beneficial for drugs exhibiting a narrow absorption window, poor bioavailability, or requiring localized action within the gastrointestinal tract. Mucoadhesion occurs through several sequential processes, including intimate contact between the formulation and mucus, polymer hydration and swelling, interpenetration of polymer and mucin chains, and formation of secondary chemical or physical interactions. Various theories have been proposed to explain the mechanism of mucoadhesion, including wetting, diffusion, adsorption, electronic, fracture, and mechanical theories. The extent and strength of mucoadhesion are influenced by several formulation and physiological factors, such as polymer molecular weight, concentration, and hydration, and charge, degree of cross-linking, mucus turnover, pH, ionic strength, and gastrointestinal motility. Different mucoadhesive dosage forms have been investigated, including tablets, microspheres, nanoparticles, films, gels, patches, and capsules. These systems can enhance drug residence time, improve drug absorption, reduce dosing frequency, and potentially increase drug plasma concentrations and therapeutic activity. Consequently, mucoadhesive drug delivery represents a promising strategy for improving the bioavailability, controlled release, and site-specific delivery of pharmaceutical agents. This review discusses the fundamental mechanisms and theories of mucoadhesion, factors affecting mucoadhesive performance, and recent developments in various mucoadhesive dosage forms.