OBJECTIVES: This systematic review was conducted to investigate the characteristics and effects of clinical decision support systems (CDSSs) on clinical and process-of-care outcomes of patients with kidney disease. METHODS: A comprehensive systematic search was conducted in electronic databases to identify relevant studies published until November 2020. Randomized clinical trials evaluating the effects of using electronic CDSS on at least one clinical or process-of-care outcome in patients with kidney disease were included in this study. The characteristics of the included studies, features of CDSSs, and effects of the interventions on the outcomes were extracted. Studies were appraised for quality using the Cochrane risk-of-bias assessment tool. RESULTS: Out of 8722 retrieved records, 11 eligible studies measured 32 outcomes, including 10 clinical outcomes and 22 process-of-care outcomes. The effects of CDSSs on 45.5% of the process-of-care outcomes were statistically significant, and all the clinical outcomes were not statistically significant. Medication-related process-of-care outcomes were the most frequently measured (54.5%), and CDSSs had the most effective and positive effect on medication appropriateness (18.2%). The characteristics of CDSSs investigated in the included studies comprised automatic data entry, real-time feedback, providing recommendations, and CDSS integration with the Computerized Provider Order Entry system. CONCLUSION: Although CDSS may potentially be able to improve processes of care for patients with kidney disease, particularly with regard to medication appropriateness, no evidence was found that CDSS affects clinical outcomes in these patients. Further research is thus required to determine the effects of CDSSs on clinical outcomes in patients with kidney diseases.