This study aimed to explore the relationship between biochemical profiles and the risk of age-related macular degeneration (AMD) through a cross-sectional observational analysis. We examined data of U. S. population from the 2005-2008 National Health and Nutrition Examination Survey (NHANES) database. Student's t-test, multivariable logistic regression, Pearson's correlation, restricted cubic spline (RCS) model, and linear regression were applied to analyze the underlying relationship between biochemical profiles and the AMD risk, through comparing data between the non-AMD and AMD subgroups. Multivariable logistic regression, adjusted for age and demographic factors, showed no significant associations between the AMD risk and the levets of specific biochemical parameters (P >
0.05). Pearson's correlation revealed a positive linear relationship between age and total bilirubin, uric acid in the non-AMD subgroup (P <
0.05), but no such liner association was found in the AMD subgroup (P >
0.05). The RCS model confirmed no non-linear relationships presented between these variables in the AMD subgroup. In addition, without age adjustment, significant associations were found between total bilirubin, uric acid, and the AMD presence (P <
0.05). Biochemical profiles, after adjusting for age, did not significantly influence the AMD risk. However, total bilirubin and uric acid might potentially be related to the AMD presence. Our findings suggest a need for further research to clarify the role of these biomarkers in AMD development.