Red cell distribution width (RDW), a widely used and non-invasive biomarker of systemic inflammation, has been linked to various inflammatory conditions, including erectile dysfunction (ED). This study investigates the relationship between RDW and other inflammation-associated biomarkers with ED, using data from the National Health and Nutrition Examination Survey (NHANES) collected between 2001 and 2004. The analysis included 3988 participants, with 29.46 % classified as having ED. Biomarkers such as RDW, monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), aggregate index of systemic inflammation (AISI), and C-reactive protein (CRP) were evaluated. Methods included multivariable logistic regression, subgroup analysis, generalized additive models (GAM), and smoothed curve fitting to explore associations. Receiver operating characteristic (ROC) curve analysis was used to assess diagnostic capabilities. Results showed significant positive associations between ED and RDW, MLR, NLR, and SIRI, with nonlinear relationships identified. RDW demonstrated the highest diagnostic accuracy for distinguishing ED (AUC = 0.66, 95 % CI: 0.65–0.68), outperforming other biomarkers. The study concludes that RDW is independently associated with ED, offering cost-effectiveness, non-invasiveness, and high diagnostic accuracy, making it a promising biomarker for ED assessment strategies.