Dry eye disease (DED) is a multifactorial condition characterized by the loss of tear film homeostasis and associated ocular symptoms. Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays a central role in the pathogenesis of DED. This review explores the intricate relationship between oxidative stress and DED, highlighting its significance in understanding the disease's progression and potential therapeutic strategies. **Key Points:** 1. **Pathogenesis of DED:** Oxidative stress leads to cellular apoptosis, inflammation, and damage to the ocular surface, exacerbating DED symptoms. 2. **Biomarkers of Oxidative Stress:** Biomarkers such as ROS, lipid peroxidation products, and antioxidant enzymes provide valuable insights into disease severity and progression. 3. **Animal and In Vitro Models:** Various animal and in vitro models have been developed to study the role of oxidative stress in DED, including transgenic, non-transgenic, and surgical intervention models. 4. **Clinical Studies:** Clinical studies have shown that oxidative stress markers are associated with DED severity and can be used to evaluate treatment efficacy. 5. **Therapeutic Approaches:** Antioxidants and antioxidant strategies, including dietary supplements and drug treatments, have shown promise in alleviating DED symptoms and reducing oxidative stress. **Conclusion:** Oxidative stress is a critical factor in the development and progression of DED. Targeting oxidative stress pathways through innovative therapeutic approaches, such as the use of antioxidants, could provide new avenues for managing DED. Future research should focus on developing novel antioxidants and understanding the natural causes of DED to improve therapeutic outcomes and enhance the quality of life for DED patients.Dry eye disease (DED) is a multifactorial condition characterized by the loss of tear film homeostasis and associated ocular symptoms. Oxidative stress, resulting from an imbalance between reactive oxygen species (ROS) production and antioxidant defenses, plays a central role in the pathogenesis of DED. This review explores the intricate relationship between oxidative stress and DED, highlighting its significance in understanding the disease's progression and potential therapeutic strategies. **Key Points:** 1. **Pathogenesis of DED:** Oxidative stress leads to cellular apoptosis, inflammation, and damage to the ocular surface, exacerbating DED symptoms. 2. **Biomarkers of Oxidative Stress:** Biomarkers such as ROS, lipid peroxidation products, and antioxidant enzymes provide valuable insights into disease severity and progression. 3. **Animal and In Vitro Models:** Various animal and in vitro models have been developed to study the role of oxidative stress in DED, including transgenic, non-transgenic, and surgical intervention models. 4. **Clinical Studies:** Clinical studies have shown that oxidative stress markers are associated with DED severity and can be used to evaluate treatment efficacy. 5. **Therapeutic Approaches:** Antioxidants and antioxidant strategies, including dietary supplements and drug treatments, have shown promise in alleviating DED symptoms and reducing oxidative stress. **Conclusion:** Oxidative stress is a critical factor in the development and progression of DED. Targeting oxidative stress pathways through innovative therapeutic approaches, such as the use of antioxidants, could provide new avenues for managing DED. Future research should focus on developing novel antioxidants and understanding the natural causes of DED to improve therapeutic outcomes and enhance the quality of life for DED patients.