Background: The impact of integrated lifestyles on health has attracted a lot of attention. It remains unclear whether adherence to low-risk healthy lifestyle factors is protective in individuals with metabolic syndrome and metabolic syndrome-like characteristics. We aimed to explore whether and to what extent overall lifestyle scores mitigate the risk of all-cause mortality in individuals with metabolic syndrome and metabolic syndrome-like characteristics. Methods: In total, 6934 participants from the 2007 to 2014 National Health and Nutrition Examination Survey (NHANES) were included. The weighted healthy lifestyle score was constructed based on smoking, alcohol consumption, physical activity, diet, sleep duration, and sedentary behavior information. Generalized linear regression models and restricted cubic splines were used to analyze the association between healthy lifestyle scores and all-cause mortality. ​ Results: Compared to participants with relatively low healthy lifestyle scores, the risk ratio (RR) in the middle healthy lifestyle score group was 0.51 (RR = 0.51, 95% CI 0.30–0.88), and the high score group was 0.26 (RR = 0.26, 95% CI 0.15–0.48) in the population with metabolic syndrome. The difference in gender persists. In females, the RRs of the middle and high score groups were 0.47 (RR = 0.47, 95% CI 0.23–0.96) and 0.21 (RR = 0.21, 95% CI 0.09–0.46), respectively. In males, by contrast, the protective effect of a healthy lifestyle was more pronounced in the high score group (RR = 0.33, 95% CI 0.13–0.83) and in females, the protective effects were found to be more likely. The protective effect of a healthy lifestyle on mortality was more pronounced in those aged < 65 years. Higher lifestyle scores were associated with more prominent protective effects, regardless of the presence of one metabolic syndrome factor or a combination of several factors in 15 groups. What's more, the protective effect of an emerging healthy lifestyle was more pronounced than that of a conventional lifestyle. Conclusions: Adherence to an emerging healthy lifestyle can reduce the risk of all-cause mortality in people with metabolic syndrome and metabolic syndrome-like characteristics; the higher the score, the more obvious the protective effect. Our study highlights lifestyle modification as a highly effective nonpharmacological approach that deserves further generalization.

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