Aims: The underlying mechanism of both sleep disorders and frailty is chronic inflammation, which can be reflected by the dietary inflammatory index (DII). Therefore, we aimed to explore the association between sleep quality, frailty, and dietary inflammation. Methods: 9007 participants aged over 20 years from the National Health and Nutrition Examination Survey (NHANES) in 2005-2008 were involved in the study. Dietary inflammation was assessed by DII, sleep quality was assessed by the Pittsburgh sleep quality index (PSQI), and frailty was assessed by the 36-item frailty index (FI). Logistic regression, stratified analysis of sub-groups, and forest plots were used in this study. Results: Both pro-inflammatory diet and poor sleep quality were risk factors for frailty. There was an interaction between dietary inflammation and sleep quality (P-interaction = 0.003). Pro-inflammatory diet was associated with increased risk of frailty among the population with poor sleep quality. Compared with the anti-inflammatory diet and good sleep quality group, the OR of frailty was 1.44 (1.21, 1.73) and 2.16 (1.64, 2.80) for the anti-inflammatory diet and poor sleep quality and pro-inflammatory diet and poor sleep quality groups, respectively. Conclusion: There was an interaction between dietary inflammation and sleep quality on frailty. Anti-inflammatory diet may attenuate the detrimental impacts of poor sleep quality on frailty.