Parallel to the increase in obesity, the prevalence of metabolic syndrome (MetS) is continually increasing, with increased risk of diabetes and cardiovascular atherosclerosis diseases. Despite the importance of this public health problem, the relative impact of diet and physical activity on MetS prevalence has yet to be established. We investigated the association between lifestyle, in terms of both habitual dietary pattern and physical activity, and MetS in a cohort of adults without known diabetes and atherosclerotic cardiovascular disease. Four hundred seventy-seven randomly selected adult participants were cross-sectionally investigated. Each participant answered a food frequency questionnaire and a questionnaire on physical activity, and underwent routine laboratory blood measurements. MetS was identified in 24.7% of the cohort. Dietary patterns were not significantly different (P = 0.31) between the groups (with or without MetS). The habitual physical activity level was significantly lower (P = 0.011) in the group with MetS. In particular, the prevalence of sedentary participants was 58.1% in the group with MetS, and 43.9% in the group without MetS. Multivariate analysis revealed that MetS was associated with age (OR = 1.06, 95% CI 1.03-1.08) and physical activity level (light vs. sedentary: OR = 0.53, 95% CI 0.32-0.87; moderate/heavy vs. sedentary: OR = 0.31, 95% CI 0.13-0.75). This study suggests that inadequate physical activity level is associated with MetS. Our results are therefore consonant with the notion of healthier lifestyle changes to counteract the epidemic of diabetes and cardiovascular disease, though adequate interventional trials will be needed in high-risk populations.