Mass spectrometry-based proteomic profiling was performed using second-trimester plasma samples from 80 singleton pregnancies, including non-PMOS term, non-PMOS sPTB, PMOS term, and PMOS sPTB groups (n = 20 per group). This study investigated phenotype-specific proteomic alterations associated with spontaneous preterm birth and identified potential circulating biomarkers. The dataset includes raw mass spectrometry files, protein and peptide identification and quantification results, and de-identified sample metadata.