Purpose : The purpose of this study was two-fold: to investigate the effects of uncertainty and depression on the quality of life (QoL) of elderly people with chronic diseases and to provide basic data on the physical, emotional, and psychological factors affecting their QoL in the field of physical therapy. Methods : A questionnaire covering uncertainty, depression, and QoL was distributed among 320 elderly people. Pearson's correlation analysis was performed to examine the correlation between uncertainty (ambiguity, complexity, inconsistency, and unpredictability), depression, and QoL (physical, psychological, social, and living environment domains) of the respondents; furthermore, multiple regression analysis was performed to identify the factors affecting the QoL of the respondents with a chronic disease. Results : The sub-factors of uncertainty and QoL-"complexity and social domain" (r=-.295, p<.001), "complexity and living environment domain" (r=-.302, p<.001), and "inconsistency and living environment domain" (r=-.360, p<.001)-showed a negative (-) correlation, as did depression and the sub-factors of QoL-"depression and physical domain" (r=-.782, p<.001), "depression and psychological domain" (r=-.876, p<.001), "depression and social domain" (r=-.668, p<.001), and "depression and living environment domain" (r=-.731, p<.001). The factors affecting QoL were complexity (𝛽=-.122, p<.001), inconsistency (𝛽=-.102, p=.002), unpredictability (𝛽=.112, p<.001), and depression (𝛽=-.850, p<.001). The relative influence of the independent variables was in the order of depression, complexity, unpredictability, and inconsistency, and the explanatory power was 77.1 % (F=215.853, p<.001). Conclusion : It is important to help the elderly with chronic diseases reduce the negative impact on their quality of life by helping them gain support from their families and medical professionals and by increasing their understanding through communication so that they can transition from negative emotions to positive emotions of opportunity.