A leaky gut can trigger chronic inflammation and poses a primary risk for metabolic diseases. This study established a relationship between intestinal integrity (leaky gut) and metabolic health in a general population. Leaky-gut markers (LGMs) were studied in a large population of Dutch adults with a broad spectrum of metabolic health. This study enrolled 500 individuals selected within the NQplus cohort study ( n = 2048) by stratified randomization, based on waist circumference, fasting glucose, and high-density lipoprotein (HDL) cholesterol to obtain a representative and balanced population in terms of metabolic health parameters, sex (male/female), and age (<54/≥54 years). LGMs—zonulin, lipopolysaccharide-binding protein (LBP), and soluble CD14 (sCD14)—were measured in EDTA plasma or serum. Zonulin was most strongly associated with metabolic health. Zonulin and LBP were most strongly associated with the inflammatory marker C-reactive protein (CRP). The quartile analysis for zonulin and LBP showed that most metabolic health parameters and CRP levels increased from Q1 to Q4, with significant differences between quartiles, except for markers related to glucose homeostasis (glucose and glycated hemoglobin A1c (HbA1c)). Associations between LGMs and metabolic health parameters in this large Dutch adult population indicate that LGMs are valuable markers for identifying people at risk of a leaky gut and subsequent chronic inflammation linked to metabolic disorders.