Damage-associated molecular patterns (DAMPs) are endogenous molecules produced in response to cellular damage or stress, which can activate the innate immune system. These DAMPs include nucleic acids, proteins, ions, glycans, and metabolites. Upon cellular damage or stress, these molecules undergo changes in distribution, physical or chemical properties, or concentration, becoming DAMPs that can be recognized by innate immune receptors, leading to inflammatory responses. This review summarizes the conversion of homeostatic molecules into DAMPs, their diverse nature and classification, cellular origin, and sensing mechanisms. It also discusses the role of DAMPs in inflammation and related diseases, as well as clinical strategies to treat DAMP-associated diseases by targeting DAMP-sensing receptors. The review highlights the importance of DAMPs in both protective immune responses and the pathogenesis of inflammatory diseases, emphasizing the need for precise control of DAMP production to maintain homeostasis and prevent disease.Damage-associated molecular patterns (DAMPs) are endogenous molecules produced in response to cellular damage or stress, which can activate the innate immune system. These DAMPs include nucleic acids, proteins, ions, glycans, and metabolites. Upon cellular damage or stress, these molecules undergo changes in distribution, physical or chemical properties, or concentration, becoming DAMPs that can be recognized by innate immune receptors, leading to inflammatory responses. This review summarizes the conversion of homeostatic molecules into DAMPs, their diverse nature and classification, cellular origin, and sensing mechanisms. It also discusses the role of DAMPs in inflammation and related diseases, as well as clinical strategies to treat DAMP-associated diseases by targeting DAMP-sensing receptors. The review highlights the importance of DAMPs in both protective immune responses and the pathogenesis of inflammatory diseases, emphasizing the need for precise control of DAMP production to maintain homeostasis and prevent disease.