Background <p>The triglyceride-glucose (TyG) index has emerged as a promising biomarker for assessing insulin resistance. Considering the impact of obesity on insulin resistance, some researchers combined TyG with body mass index (BMI), waist circumference (WC), waist-height ratio (WHtR) and other anthropometrics and used these to predict metabolic disease. Weight-adjusted waist index (WWI) was considered to be a more accurate parameter of obesity than other anthropometrics, but no studies have combined WWI with TyG index.</p> Aims <p>To investigate whether TyG-WWI was superior to other indices in assessing diabetes risk and mortality risk.</p> Methods <p>This study utilized data from the National Health and Nutrition Examination Survey. A total of 19,894 participants were included. TyG-WWI and other TyG-derived indices were calculated, and their associations with diabetes mellitus (DM), All-cause mortality, cardiovascular disease (CVD) mortality, and DM-related mortality were evaluated using logistic regression, Cox regression, and receiver operating characteristic curve (ROC) analysis.</p> Results <p>TyG-WWI was positively associated with the risk of DM (OR: 1.11, 95%CI: 1.10–1.12, <i>P</i> &lt; 0.001) and various mortality outcomes, including All-cause mortality (HR: 1.02, 95%CI: 1.01–1.02, <i>P</i> &lt; 0.001), CVD mortality (HR: 1.01, 95%CI: 1.01–1.02, <i>P</i> = 0.014), and DM-related mortality (HR: 1.04, 95%CI: 1.01–1.08, <i>P</i> = 0.013). ROC showed that TyG-WWI had the largest area under the curve for predicting DM (AUC: 0.81, 95% CI: 0.80–0.81), All-cause mortality (AUC: 0.69, 95% CI: 0.68–0.70), CVD mortality (AUC: 0.71, 95% CI: 0.69–0.72), and DM-related mortality (AUC: 0.85, 95% CI: 0.82–0.89) compared to other TyG-derived indices.</p> Conclusions <p>TyG-WWI demonstrates superior predictive accuracy for DM and mortality risks compared to the standalone TyG index and other TyG-derived indices.</p>