Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with limited early diagnostic methods and therapeutic options, contributing to its poor prognosis. Recent advances in high-throughput sequencing have highlighted the critical roles of noncoding RNAs (ncRNAs), particularly PIWI-interacting RNAs (piRNAs), in cancer biology. In this review, we systematically summarize the emerging roles of piRNAs and their associated PIWI proteins in PDAC pathogenesis, progression, and prognosis. We provide a comprehensive analysis of the molecular mechanisms by which piRNAs/PIWIs regulate gene expression and cellular signaling pathways in PDAC. Furthermore, we discuss their potential as novel biomarkers for early diagnosis and therapeutic targets. Importantly, this review identifies key piRNAs/PIWIs involved in PDAC and proposes innovative strategies for improving diagnosis and treatment outcomes. Our work not only consolidates current knowledge but also offers new perspectives for future research and clinical applications in PDAC management.