Background <p>The novel serum C-reactive protein–triglyceride glucose index (CTI) represents a novel integrative biomarker for inflammation and insulin resistance. Despite this, its association with anxiety status remains underexplored.</p> Aim <p>This study aims to investigate the relationship between the C-reactive protein–triglyceride glucose index (CTI) and anxiety status.</p> Methods <p>Data were obtained from the National Health and Nutrition Examination Survey database 2007–2010. Associations between CTI (continuous and quartiles) and anxiety outcomes were evaluated using weighted multivariable logistic regression for anxiety status (odds ratios, ORs) and linear regression for anxiety days (β coefficients). RCS regression analysis was employed to model the relationship between CTI and anxiety. Subgroup analysis has been performed to examine potential effect modifications.</p> Results <p>Baseline attributes of the nationally representative cohort (weighted <i>N</i> = 172,699,334; unweighted <i>n</i> = 3876) are detailed. Anxiety prevalence reached 25.6% after weighting. Within fully adjusted Model 3, per-unit CTI elevation maintained a positive anxiety association (OR = 1.24, 95% CI 1.08–1.42, <i>p</i> = 0.006). Only participants in the highest CTI quartile (Q4) showed significantly elevated anxiety risk (OR: 1.31, 95% CI 1.02–1.70, <i>P</i> = 0.038) and anxiety days (<i>β</i>: 1.23, 95% CI 0.21–2.25, <i>P</i> = 0.02) compared to Q1, with significant positive trends (<i>P</i> = 0.028 and 0.019, respectively). Smoothed curve fitting coupled with threshold effect analysis revealed a nonlinear CTI–anxiety relationship. Subgroup and sensitivity assessments confirmed stable CTI–anxiety connections throughout population strata.</p> Conclusion <p>This study highlights a significant association between C-reactive protein–triglyceride glucose index and anxiety status in the NHANES population. Future research should validate its clinical utility for risk stratification and public health interventions.</p>