As a significant health challenge, chronic disease can have critical spiritual consequences for patients. Therefore, the study of spiritual well-being as an aspect of health is essential but has been less considered with regard to chronic diseases. Thus, this systematic review and meta-analysis were conducted to investigate spiritual well-being in patients with chronic diseases. For this purpose, in the initial search that was performed of valid databases, a total of 615 descriptive studies published between 2000 and 2018 were found. After carefully assessing these, only 24 studies were included in the review. Overall, the spiritual well-being of 3289 patients with chronic disease was investigated. This study showed that the total mean score of the spiritual well-being of patients with chronic diseases was 86.65 (P < 0.001, 95%, CI: 80.34-92.96), indicating a moderate level of spiritual well-being in these patients. Thus, patients with chronic diseases are recommended to consider spiritual consultation programs.