Background <p>Gut microbes are important for the development of atherosclerotic cardiovascular disease (ASCVD), and the dietary index for gut microbiota (DI-GM), a new measure of gut flora-friendly diets, has not been systematically investigated in relation to ASCVD.</p> Objective <p>This study aimed to evaluate the correlation between DI-GM and the risk of ASCVD in American older adults, also to analyze the mediating role of body mass index (BMI).</p> Methods <p>Researchers selected 2234 elderly participants ≥ 65 years of age from the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2018 for a cross-sectional cohort study. Stratified analyses were taken based on DI-GM quartile. To achieve our research objectives, we employed logistic regression analysis, smooth curve fitting, interaction effects analysis, and mediation analysis.</p> Results <p>After adjusting for confounders, individuals with higher DI-GM had a significantly lower risk of ASCVD (highest quartile vs. lowest quartile OR = 0.73, 95% CI: 0.52–1.01, P &lt; 0.001). DI-GM was linearly negatively associated with ASCVD (P = 0.13) and the association was stable in the diabetes subgroup (interaction P &gt; 0.05), but age, gender and BMI may modify the association between DI-GM and ASCVD (interaction P &lt; 0.05). BMI mediated 11.51% of the association between DI-GM and ASCVD (95% CI: 2.54%-54.1%, P = 0.016).</p> Conclusion <p>DI-GM is likely to be a promising indicator for the assessment of the risk of ASCVD, with BMI exhibiting a partial mediating effect in this association. Future studies should prioritize a comprehensive investigation of the underlying mechanisms by which DI-GM contributes to atherogenesis, with the aim of enhancing the efficacy of early prevention strategies for ASCVD.</p>