Lysine lactylation of (Kla), a newly recognized post-translational modification of proteins, is prevalent in various diseases and is increasingly attracting interest. The multifaceted roles of Kla are being revealed, demonstrating a complex ‘double-edged sword’ effect in different disorders, which is influenced by site-specific modifications and other factors. Recent studies have underscored the therapeutic potential of Kla in the treatment of a range of disorders. This review examines the current status of research on drugs and other compounds that may affect the role of Kla in disease. It also considers alternative approaches to therapy. The differential effects of Kla and its inhibitors in disease models are assessed, and therapeutic strategies that harness Kla as a treatment mechanism are suggested. Furthermore, the review explores the therapeutic promise of Kla targets in managing disorders, providing a scientific basis and a roadmap for subsequent research and drug development.