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