Background <p>Serum albumin is a key biomarker of nutritional and health status, but its relationship with constipation remains unclear. This study aimed to investigate the association between serum albumin levels and constipation prevalence in a nationally representative population.</p> Methods <p>A cross-sectional analysis of 11,092 adults from the National Health and Nutrition Examination Survey (NHANES 2005–2010) was performed. Serum albumin was analyzed as both a continuous and quartile variable. Weighted logistic regression, restricted cubic spline models, subgroup analyses, interaction effect analyses, and multiple propensity score methods were applied to evaluate and validate the associations.</p> Results <p>The overall prevalence of constipation was 9.9%. Higher serum albumin levels were inversely associated with constipation prevalence (unadjusted OR = 0.53, 95% CI: 0.43–0.65; fully adjusted OR = 0.75, 95% CI: 0.59–0.95). Participants in the highest quartile (Q4) had significantly lower constipation prevalence compared with those in Q1 (P for trend = 0.016). Restricted cubic spline analysis confirmed a linear negative association (P for overall = 0.043; P for non-linearity = 0.768). Subgroup and interaction analyses showed consistent results, with no significant effect modifications. Sensitivity analyses using various propensity score methods supported the robustness of the findings.</p> Conclusions <p>Elevated serum albumin levels are associated with a reduced prevalence of constipation in US adults. These results suggest serum albumin may serve as a potential nutritional indicator for early risk assessment and preventive strategies.</p>