National prevalence of diabetes distress is unknown among US adults. This cross-sectional study examined the prevalence among US adults with diabetes using 2021 National Health Interview Survey data. Multivariable multinomial logistic regressions were used to estimate adjusted prevalence and prevalence ratios for diabetes distress. Adjusted prevalence of moderate and severe diabetes distress was 24.3% (95% CI, 22.5%-26.1%) and 6.6% (95% CI, 5.6%-7.8%), respectively. Prevalence was higher among people aged 18 to 64 years, women, and those with lower incomes. Findings highlight the importance of examining economic and social factors and integrating diabetes distress screening into diabetes management and services.