The novel inflammatory markers neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immunoinflammatory index (SII) have not yet been used in the study of age-related cataracts. The aim of this study was to investigate the possible relationships between the NLR, PLR, and SII and age-related cataracts. In the 2005-2008 National Health and Nutrition Examination Survey (NHANES) cross-sectional surveys, we collected complete information on blood counts, whether cataract surgery had been performed, and baseline information for adults. We investigated the independent interactions between the inflammatory markers NLR, PLR, and SII and age-related cataracts via weighted multivariate regression analyses and subgroup analyses. Smoothed curve fitting was performed to identify nonlinear associations and saturation effects between inflammation indices and cataract risk. Finally, receiver operating characteristic (ROC) curves were plotted for factors significantly associated with the development of cataracts to identify the optimal diagnostic inflammation index. This study included 8887 participants without cataracts and 935 participants with cataracts. Multivariate logistic regression analyses after adjusting for covariates revealed that a high SII (OR = 1.000, 95% CI = 1.000-1.000; P = 0.017) and high NLR (OR = 1.065, 95% CI = 1.000-1.134; P = 0.048) were independent risk factors for cataracts. Subgroup analyses did not reveal interactions between the SII, NLR, or cataract and covariates. Smoothed curve fits of the relationships between the SII or NLR and cataracts did not show positive significant saturating effect values for any of the variables. The ROC curve revealed some diagnostic value for cataracts for both the SII (AUC = 0.549, P < 0.001) and the NLR (AUC = 0.603, P < 0.001), but both had weak diagnostic value. Our study suggests that the SII and NLR are independent risk factors for cataracts in U.S. adults, but no such associations was identified between the PLR and cataracts.