Histone lactylation, as a common post-translational modification (PTM), is crucial in diseases. Aberrant histone lactylation has been linked to disease pathogenesis, thus positioning it as a therapeutic target. This review summarizes the bidirectional relationship between histone lactylation and diseases, emphasizing how Traditional Chinese medicine (TCM) regulates lactate levels to restore histone lactylation homeostasis. Mechanistically, TCM modulates histone lactylation through dual regulation of lactyltransferases and lactate metabolism, thereby influencing disease progression in inflammatory, metabolic, and neoplastic disorders. Notably, TCM is characterized by unique advantages of cost-effectiveness, high efficacy, and minimal adverse effects. For diseases with established drug resistance, TCM offers a promising therapeutic alternative in managing drug-resistant illness by regulating histone lactylation. This review is conducive to understanding the relationship between histone lactylation and disease. TCM effectively treats diseases through the regulation of histone lactylation, thereby highlighting its potential for disease treatment application.