<p>Serum uric acid levels may influence depressive symptoms. Our study aimed to investigate the age-dependent association between serum uric acid levels and depressive symptoms in adults, using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. Weighted multivariate logistic regression models were employed to assess the association between uric acid levels and depressive symptoms. A rolling window model (20-year window) was applied to explore age-related trends in odds ratios (ORs), leading to age stratification: &lt; 40 years and ≥ 40 years. The ORs of uric acid in the two age groups were calculated using two different multinomial logistic regression models that adjusted for age, gender, race and no variables, respectively. Finally, we applied the Games-Howell test to compare the differences in bootstrap ORs between different uric acid groups. No significant association was found between uric acid and depressive symptoms in subjects aged below 40. Among subjects aged 40 and above, the moderate uric acid levels (315.2–374.7 µmol/L) were associated with lower odds of depressive symptoms (<i>OR</i> = 0.78, 95% CI 0.63–0.98, <i>P</i> &lt; 0.05). After adjustment, the high uric acid levels (≥ 374.7 µmol/L) were associated with higher odds of depressive symptoms (<i>OR</i> = 1.31, 95% CI 1.04–1.67, <i>P</i> &lt; 0.05). A trend of increasing ORs with higher uric acid levels was observed. High uric acid levels (≥ 374.7 µmol/L) were associated with increased odds of depressive symptoms in individuals aged ≥ 40 years.</p>