<p>Atopic dermatitis has complex pathological mechanisms involving systemic inflammation. This study aimed to explore the associations between common hematological biomarkers—neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil percentage-to-albumin ratio (NPAR)—and the risk of atopic dermatitis within a population-based cohort. Data from 9,262 individuals (20–59 years old) were analyzed using the National Health and Nutrition Examination Survey (NHANES) 2001–2006 cycles. Logistic regression models, restricted cubic spline, two-piecewise linear regression model, interaction analysis and subgroup analysis were used to assess the associations between NLR, PLR, NPAR, and atopic dermatitis. In this study of 9,262 individuals aged 20–59 years from NHANES 2001–2006, we found that NLR and PLR were positively associated with atopic dermatitis risk. The NLR and PLR values were significantly higher in individuals with atopic dermatitis compared to those without. Logistic regression analysis confirmed that NLR and PLR were independently associated with an increased risk of atopic dermatitis after adjusting for covariates. We also observed a nonlinear relationship between NLR, NPAR and atopic dermatitis, with threshold effects at 1.92 for NLR and 1.87 for NPAR. Subgroup analyses showed that male, lower BMI, and drinking were associated with higher atopic dermatitis risk. These findings highlight the potential of NLR and PLR as clinical biomarkers for atopic dermatitis risk assessment. NLR and PLR may serve as potential clinical biomarkers for atopic dermatitis risk assessment due to their significant associations and cost-effective measurement.</p>