BackgroundDaily diet represents a potentially modifiable factor in the development of depression. However, to date, no studies have investigated the impact of dietary active microorganisms on depressive symptoms. The aim of this study is to explore the relationship between these two factors. MethodsPopulation data from NHANES 2005–2018 indicated that the exposure variable was dietary intake of active microbes, while the outcome variable was depression as defined by a 9-item Patient Health Questionnaire (PHQ-9) score. A multivariate logistic regression model was employed to assess the impact of dietary living microbe intake on depression symptoms. ResultsA total of 19,169 American adults with a mean age of 46.89 years (SD = 16.97) were included in this cross-sectional analysis; among them, 53.84 % were male and 8.11 % (n = 1555) met the criteria for depression symptoms. In the fully adjusted model, patients with medium and high dietary living microbe intake exhibited a significant reduction in depression symptoms prevalence by 28 % (OR, 0.72; 95 % CI: 0.64–0.81) and 26 % (OR, 0.74; 95 % CI: 0.63–0.85), respectively, compared to those with low dietary living microbe intake. Subgroup analyse indicate that no significant interaction was observed between dietary living microbe intake group and subgroups. ConclusionHigher intake of active microbes in the diet was found to have a negative correlation with depression.