This article explores the cellular and molecular mechanisms of epithelial tissue regeneration during inflammation and highlights its clinical significance across multiple organ systems. Epithelial repair is mediated through coordinated activation of resident stem and progenitor cells, dedifferentiation of mature epithelial cells, restitution-driven migration, extracellular matrix remodeling, and tightly regulated cytokine signaling. The interplay between epithelial and mesenchymal compartments, along with key pathways such as NF-κB, STAT3, Wnt/β-catenin, Notch, and TGF-β, determines whether regeneration proceeds toward healthy restoration or pathological remodeling. The article emphasizes how chronic inflammation disrupts regenerative balance, contributing to metaplasia, fibrosis, barrier dysfunction, and inflammation-associated carcinogenesis. Understanding these processes provides a foundation for therapeutic strategies aimed at improving mucosal healing and epithelial repair in dermatological, gastrointestinal, respiratory, and regenerative-medicine contexts.