Dry eye disease (DED) refers to a condition characterized by reduced stability of the tear film or an imbalance in the microenvironment of the ocular surface, resulting from abnormalities in tear quality, quantity and kinetics. This condition leads to various ocular discomforts and even visual impairment. The pathogenesis of DED is multifactorial and current treatment options mainly focus on symptom relief and preservation of visual function. Acupuncture has shown effectiveness in treating dry eye, although its underlying mechanism of action remains incompletely understood. Investigating the regulatory mechanisms involved in acupuncture intervention can provide a theoretical basis for acupuncture treatment research and contribute to the understanding of its effects at a fundamental level. Proteomics technology offers a comprehensive and systematic approach to studying the functions, structures and interactions of proteins. Its application in DED research can provide valuable insights into the dynamic changes in protein levels associated with different etiological processes of DED and facilitate the identification of potential biomarkers. Furthermore, proteomics can systematically explore the regulatory mechanisms underlying acupuncture treatment for DED. By integrating proteomics technology into DED research, we can uncover novel perspectives and enhance our understanding of this condition. This paper aims to explore the potential application of proteomics in both clinical and basic research on DED. Ultimately, it strives to offer scientific and effective strategies for the treatment of DED and advance our knowledge of the mechanisms underlying acupuncture therapy.