BACKGROUND/OBJECTIVES: Telomere length is influenced by inflammation, insulin resistance, and hyperinsulinemia, which can be modulated by dietary factors. Nevertheless, it is still uncertain if diets with greater insulinemic or inflammatory potential are linked to shorter telomere length. SUBJECTS/METHODS: This cross-sectional study analyzed the data from the National Health and Nutrition Examination Survey in the US. A total of 6,981 individuals were included, with an average age of 46.87 ± 0.36 yrs, and a female-to-male ratio of 1.12:1. Diet was obtained using 24-h recall. Three empirical dietary indices were developed, including the Empirical Dietary Inflammatory Pattern (EDIP), which identifies foods predictive of inflammation markers such as C-reactive protein and leukocyte count; the Empirical Dietary Index for Insulin Resistance (EDIR), which assesses insulin resistance via homeostatic model assessment; and the Empirical Dietary Index for Hyperinsulinemia (EDIH), which relates to hyperinsulinemia indicators including insulin and C-peptide. Relative telomere length (RTL) was measured by quantitative polymerase chain reaction. Percentage change (%), odds ratio (OR), and their 95% confidence intervals (CIs) were evaluated using linear and ordinal logistic regression, respectively. RESULTS: EDIR (per 1 - SD increase, percentage change = -0.99%, 95% CI, -1.83%, -0.15%, = 0.022; OR, 1.08, 95% CI, 1.01, 1.16, = 0.018) and EDIH (percentage change = -1.03%, 95% CI, -1.94%, -0.11%, = 0.030; OR, 1.07, 95% CI, 1.00, 1.15, = 0.047) were associated with shorter RTL. EDIP showed a negative association with telomeres in ordinal logistic regression (OR, 1.07, 95% CI, 1.00, 1.15, = 0.038), and this inverse association was more pronounced among participants with a light or vigorous activity in both regression ( = 0.003; < 0.001). CONCLUSION: Diets high in inflammation or insulinemic potential are associated with shorter RTL. The impact of EDIP is greater in individuals engaged in light or vigorous activity.