Preterm labor is a serious issue that can lead to preterm birth, posing significant risks to both the mother and the neonate. Despite the high incidence of approximately 15 million preterm births worldwide per year, there is a lack of sufficient strategies for predicting and preventing preterm labor. Here, we found that exosomal miRNAs in maternal vaginal discharge can serve as biomarkers for early diagnosis of life-threatening conditions in both the mother and neonate. Our non-invasive biopsy of vaginal discharge using a swab allows us to isolate enriched exosomes via an advanced microfluidic platform called BEST (Biologically intact Exosome Separation Technology). We have identified specific miRNAs differentially expressed in mothers with preterm labor compared to those with full-term mothers. These miRNAs included hsa-miR-206, which was up-regulated in preterm labor, and hsa-miR-3674, hsa-miR-365a-5p, and hsa-miR-193b-3p, which were down-regulated. We believe our discovery of unique miRNAs as biomarkers can aid in early detection and effective treatment of preterm labor, potentially revolutionizing global healthcare.