Dry eye disease causes eye discomfort in patients due to lack of tears or instability of the tear film and has a prevalence of 30%-50% in Asia. Conventional therapies suffer from limited efficacy and frequent drug administration, leading to continued active research and development of new drugs. This research explores the development process of 12 new dry eye drugs from 2003 to 2023, and analyzes the key successes and failures of these drugs in the context of U.S. Food and Drug Administration(FDA) guidelines. The study found that the core strategies of successful drugs included flexible adjustment of phase Ⅲ endpoints, strict adherence to one of the three FDA efficacy targets, and consistency between phase Ⅱ and phase Ⅲ trial designs. Failure cases were mostly due to deficiencies in the design of phase Ⅱ trials, such as overestimation of the efficacy of the drug due to small samples and lack of a placebo control, which led to an insufficient sample size for phase Ⅲ trials, and also due to the failure of the drug because of failure of endpoints to be adjusted in a timely manner. Dry eye drug development should be based on rigorous phase Ⅱ clinical trials, prioritize objective endpoint indicators such as the Schirmer test in phase Ⅲ studies, and set up an run-in period to reduce the placebo effect, as well as to meet the FDA's requirements on sample size and endpoint indicators, so as to effectively reduce the risk of research and development and improve the success rate of drug marketing.