Glycosylation is a process where proteins or lipids are modified with glycans. The presence of glycans determines the structure, stability, and localization of glycoproteins, thereby impacting various biological processes, including embryogenesis, intercellular communication, and disease progression. Glycans can influence stem cell behavior by modulating signaling molecules that govern the critical aspects of self-renewal and differentiation. Furthermore, being located at the cell surface, glycans are utilized as markers for stem cell pluripotency and differentiation state determination. This review aims to provide a comprehensive overview of the current literature, focusing on the effect of glycans on stem cells with a reflection on the application of synthetic glycans in directing stem cell differentiation. Additionally, this review will serve as a primer for researchers seeking a deeper understanding of how synthetic glycans can be used to control stem cell differentiation, which may help establish new approaches to guide stem cell differentiation into specific lineages. Ultimately, this knowledge can facilitate the identification of efficient strategies for advancing stem cell-based therapeutic interventions.