Post-translational modifications (PTMs) are crucial for regulating protein functions. As a novel PTM, lactylation has emerged as a recent research hotspot, participating in pathological processes such as tumor progression and inflammation; it dynamically regulates gene expression and protein activity, which is significant for metabolic-immune coordination. In degenerative osteoarthropathy (such as osteoarthritis and rheumatoid arthritis), cartilage metabolic imbalance is closely associated with dynamic changes in lactylation, involving pathological links such as cartilage matrix degradation, synovial inflammation, and abnormal bone remodeling. Current clinical interventions cannot block disease progression. This review systematically summarizes the molecular mechanisms of lactylation (including lactate metabolism as well as histone and non-histone lactylation), regulatory factors (enzymes, environment, and molecular tools), and its role in degenerative osteoarthropathy, covering expression changes in cartilage tissues, correlation with arthritis progression, and biomarker studies in clinical models. Lactylation affects joint degeneration by regulating glycolysis-oxidative phosphorylation balance, inflammatory factor expression, and extracellular matrix metabolism. Targeted regulation strategies (such as CRISPR editing and small-molecule inhibitors) hold promise as novel therapeutic approaches. Future research needs to overcome technical limitations in detection, decipher the dynamic lactylation network through interdisciplinary collaboration, and promote its clinical translation in early diagnosis, precise intervention, and personalized treatment.