Damage-associated molecular patterns (DAMPs) are endogenous molecules released from damaged or dying cells that activate the innate immune system by interacting with pattern recognition receptors (PRRs). While DAMPs help defend the host, they can also promote pathological inflammation. Recent studies have shown that DAMPs such as HMGB1, S100 proteins, and HSPs play a pathogenic role in inflammatory diseases. This review discusses the role of DAMPs in inflammatory diseases, including rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, atherosclerosis, Alzheimer's disease, Parkinson's disease, and cancer. It also explores the potential of DAMPs as biomarkers and therapeutic targets for these diseases. DAMPs are involved in various inflammatory processes, including the activation of TLRs, NLRP3 inflammasomes, and other PRRs. They contribute to the progression of diseases by inducing inflammation and modulating immune responses. DAMPs can originate from extracellular or intracellular sources and include proteins such as HMGB1, S100 proteins, HSPs, and plasma proteins. The regulation of DAMP signaling may offer therapeutic strategies for inflammatory diseases. However, the exact mechanisms and interactions between DAMPs and PRRs remain areas of ongoing research. This review highlights the complex roles of DAMPs in inflammatory diseases and their potential as therapeutic targets.Damage-associated molecular patterns (DAMPs) are endogenous molecules released from damaged or dying cells that activate the innate immune system by interacting with pattern recognition receptors (PRRs). While DAMPs help defend the host, they can also promote pathological inflammation. Recent studies have shown that DAMPs such as HMGB1, S100 proteins, and HSPs play a pathogenic role in inflammatory diseases. This review discusses the role of DAMPs in inflammatory diseases, including rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, atherosclerosis, Alzheimer's disease, Parkinson's disease, and cancer. It also explores the potential of DAMPs as biomarkers and therapeutic targets for these diseases. DAMPs are involved in various inflammatory processes, including the activation of TLRs, NLRP3 inflammasomes, and other PRRs. They contribute to the progression of diseases by inducing inflammation and modulating immune responses. DAMPs can originate from extracellular or intracellular sources and include proteins such as HMGB1, S100 proteins, HSPs, and plasma proteins. The regulation of DAMP signaling may offer therapeutic strategies for inflammatory diseases. However, the exact mechanisms and interactions between DAMPs and PRRs remain areas of ongoing research. This review highlights the complex roles of DAMPs in inflammatory diseases and their potential as therapeutic targets.