PurposePrevious studies have shown higher cardiovascular mortality risk with higher monocyte–lymphocyte ratio levels in general population. However, the levels of oxidative stress in individuals with type 2 diabetes are higher than those in the general population, which may affect the link between monocyte‐to‐lymphocyte ratio and cardiovascular disease deaths. And the association between the monocyte‐to‐lymphocyte ratio and mortality risk in people with type 2 diabetes still be unknown. This study aimed to investigate the prognostic significance of monocyte‐to‐lymphocyte ratio in type 2 diabetes.MethodsThis analysis involved 2,954 individuals with type 2 diabetes from the National Health and Nutrition Examination Survey 1999–2010. The National Death Index records through December 31, 2019, was used to determine all‐cause and cardiovascular mortality. The prognostic roles were determined using Cox regression models, restricted cubic spline analysis, and time‐dependent receiver operating characteristic curve analysis.ResultsDuring an average follow‐up period of 12.4 years, a total of 1,007 deaths occurred, while 252 were due to cardiovascular disease. An elevated monocyte‐to‐lymphocyte ratio level exhibited a significant dose–response relationship with an increased risk of all‐cause mortality (1.34 [95% CI 1.12, 1.60] for all‐cause mortality [P trend = 0.001]). The multivariable‐adjusted HR was 1.81 (95% CI 1.25, 2.63) (P trend = 0.001) for cardiovascular mortality indicating a U‐shaped relationship (P nonlinear = 0.013).ConclusionsThe results of this study indicate a U‐shaped relationship between the monocyte‐to‐lymphocyte ratio and cardiovascular mortality in individuals with diabetes. Both very low and high monocyte‐to‐lymphocyte ratio monocyte‐to‐lymphocyte ratio values were found to be associated with increased cardiovascular mortality risk.