<p>Premature ovarian insufficiency (POI) is a significant clinical challenge leading to amenorrhea and infertility in young women. While its etiology is complex, recent research has highlighted aberrant protein glycosylation as a novel and crucial pathogenic mechanism. This review aims to synthesize current knowledge on how defects in protein glycosylation contribute to POI. We systematically explore how mutations in key glycosylation-related genes disrupt ovarian folliculogenesis and steroidogenesis. Specifically, we discuss the mechanistic roles of glycosylation defects in impairing gonadotropin signaling, extracellular matrix dynamics, and oocyte-granulosa cell interactions. Emerging evidence pointing to specific glycoforms as potential diagnostic biomarkers and therapeutic targets is also examined. Finally, we consider the translational potential of innovative strategies, such as glycomics-based diagnostics and CRISPR-mediated gene correction, for managing POI. By integrating insights from glycobiology and reproductive medicine, this review underscores the importance of glycosylation pathways in ovarian health and advocates for their inclusion in future research and clinical evaluation of POI.</p>