Calcium-calmodulin (CaM)-dependent protein kinase IIα (CaMKIIα) is a central player of molecular memory and cognitive function. It is stimulated by Ca2+/CaM binding and subsequently generates Ca2+-independent autonomous activity. Multiple signaling pathways have been shown to regulate the expression and activity of CaMKIIα. However, the mechanisms by which CaMKIIα controls long-term potentiation (LTP) or long-term depression (LTD), which are involved in learning and memory, remain obscure. Our recent study found that the expression of the CaMKIIα can be regulated by microRNAs (miRNAs). To further explore the association of miRNAs and cognitive function, we investigated the association between academic performance, cognitive ability as measured by the Inquiry for Scientific Thinking, Analytics, and Reasoning test, and plasma miRNA profiling in 669 junior high school students. Our analysis identified 38 differentially expressed miRNAs between students with high and low academic performance. Notably, miR-548e/628/885 and miR-30a/30c-1/195/204 potentially targeted genes associated with the CaMKIIα/SIRT1 signaling pathway, a crucial facilitator of memory consolidation. Furthermore, plasma levels of miR-30a, miR-30c-1, miR-195, and miR-204 exhibited significant correlations with cognitive ability and academic performance. Collectively, our findings suggest that specific plasma miRNAs, particularly the CaMKIIa/SIRT1-related miR-30a/30c-1/195/204 cluster, can serve as potential biomarkers of cognitive function in adolescents.