Objective: To establish a complete workflow of digital design and manufacturing occlusal splint for sleep bruxism, which can be preliminarily applied in clinical use, thus observe the clinical efficacy. Methods: Twenty-four patients with sleep bruxism were recruited in the study and randomly divi-ded into two groups by using random number tables. Digital-occlusal-splint (experimental group) treatment plan and traditional-occlusal-splint (control group) treatment plan were carried out for each group, respectively. For experimental group, digital models of patients’ both dental arches and the occlusion relationship after elevation were captured using an intraoral scanner. The occlusal splint was carried out by computer aided design/computer aided manufacturing (CAD/CAM), including splint designing and milling. For control group, the traditional soft occlusal splint was fabricated by vacuum laminator. The two kinds of occlusal splints were tried in the patients from each group, and the occlusal contacts were tested respectively by T-scan analysis system, which recorded the changes of occlusal indicators in the two groups. The retention, appearance and occlusal comfort degree were evaluated by the two groups of patients. Mann-Whitney test was performed with IBM SPSS 20.0 software, and bilateral test was performed. P<0.05 was considered to be statistically significant. Results: The complete workflow of digital design and manufacturing occlusal splint was successfully established. During the clinical use, there was no statistical difference in the retention evaluation of two kinds of occlusal splints between the two groups of patients (Z=-0.538, P=0.590). The appearance score (Z=2.038, P=0.042) and the occlusal comfort score (Z=-2.579, P=0.010) of the experimental group were higher than those of the control group, with statistically significant differences. The T-scan analysis results showed that only the second molar on both sides of the traditional occlusal splint had occlusal contact in intercupsal position, while the digital occlusal splint had stable and bilaterally balanced contact between the maxillary and mandibular teeth. Furthermore, the occlusal force was uniformly distributed in the experimental group. Conclusion: The complete workflow of digital occlusal splint improves the occlusal design, greatly simplifies and optimizes the traditional process of making occlusal splint. This new method is resource-saving and environmental-friendly, and it is able to serve patients more conveniently and efficiently.