Abstract Background MicroRNAs (miRNAs) are endogenous small RNAs of 21–25 nucleotides that post-transcriptionally regulate gene expressions. Recently, circulating miRNAs have been reported as promising biomarkers for neurodegenerative disorders and processes affecting the central nervous system. This study was conducted to investigate the potential role of serum miRNAs as diagnostic biomarkers for Alzheimer's disease (AD). Methods Serum samples were obtained from 105 probable AD patients and 150 age- and gender-matched normal controls. The serum concentrations of miRNAs miR-9, miR-29a, miR-29b, miR-101, miR-125b, and miR-181c were measured with a real-time quantitative reverse transcriptase PCR (qRT-PCR) method. Results We found both miR-125b and miR-181c were down-regulated while miR-9 was up-regulated in serum of AD patients compared with that of normal controls. Among the receiver operating characteristic (ROC) results, miR-125b alone showed its priority with a specificity up to 68.3% and a sensitivity of 80.8%. Importantly, miR-125b was correlated with the Mini Mental State Examination (MMSE) in AD patients. Conclusions Our results indicate that serum miR-125b may serve as a useful noninvasive biomarker for AD.