Purpose: Nutritional status and depression are major factors that affect older adults’ the quality of life (QoL). This study aimed to examine the mediating effects of depression on the relationship between nutritional status and physical and mental QoL in older adults and to provide a foundation for developing an effective nursing intervention program to improve QoL. Methods: This study used a cross-sectional, correlational study. A convenience sample of 154 older adults was recruited from J Province, South Korea, between December 2019 and August 2020. Data were analyzed using PROCESS macro with a 95% bias-corrected bootstrap confidence interval for the SPSS/WIN 25.0 program. Results: QoL positively correlated with nutritional status and negatively correlated with depression. After controlling for general covariates, depression partially mediated the relationship between nutritional status and QoL in older adults [physical QoL (Effect=0.41, 95% CI = 0.08–0.81), mental QoL (Effect=0.38, 95% CI = 0.04–0.79)]. Conclusion: Health promotion strategies are needed for older adults with poor nutritional status and high levels of depression. Additionally, nutritional status and depression in older adults affect QoL, with depression affecting QoL through nutritional status as a mediator. Therefore, interventions to improve the nutritional status and reduce depression among older adults must be developed and implemented.