BACKGROUND: Polyphenols, including flavonoids, have been the focus of numerous studies that have revealed diverse health benefits. MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that function as posttranscriptional regulators of gene expression. miRNAs can be detected in the blood and these so-called circulating miRNAs are potential biomarkers of various diseases. This study aimed to explore circulating miRNAs in plasma as a means to predict the biological effects of functional food ingredients. METHODS AND RESULTS: We used miRNA microarray analysis to compare plasma miRNA levels in mice orally administered three flavonoids (daidzein, quercetin, and delphinidin). Several miRNAs were differentially expressed in plasma from mice in each treatment group compared with the vehicle-treated group. The plasma levels of miR-25-5p, miR-146b-5p, and miR-501-3p were increased in the flavonoid-treated and the plasma levels of miR-148b-3p, miR-669e-5p, and miR-3962 were decreased. CONCLUSIONS: Our findings suggested that flavonoids alter miRNA expression in plasma and identified promising plasma miRNAs for assessing the functionality of flavonoids.