<p>Pullulan, a polysaccharide polymer made by <i>Aureobasidium pullulans</i>, has drawn a lot of interest because of its special physicochemical characteristics as a stabilizing excipient in lyophilized biologics. Because of its superior film-forming capabilities, low immunogenicity, water solubility, and biocompatibility, it is a perfect choice for improving the stability of monoclonal antibodies, vaccines, and protein-based treatments during the freeze-drying process. Pullulan, in contrast to traditional stabilizers like sucrose and trehalose, provides better defense against protein aggregation, oxidative stress, and moisture-induced degradation, maintaining the biologics’ structural integrity and bioactivity. Despite its benefits, there are a number of difficulties when using pullulan in lyophilization. Reconstitution time and product stability under different storage circumstances may be affected by its high viscosity and hygroscopic nature. Furthermore, their structure may change due to interactions with certain biologics, requiring careful formulation optimization. Additional barriers to its broad use in pharmaceutical formulations include cost, batch-to-batch variability, and regulatory concerns. To get around these restrictions, promising options are provided by developments in polymer engineering and formulation techniques, such as hybrid excipient systems and pullulan derivatives. Pullulan is a crucial stabilizing excipient in lyophilized biologics, and this study examines its benefits over conventional cryoprotectants and lyoprotectants. The difficulties in formulating it, characterisation methods, and regulatory viewpoints are also covered, offering suggestions for future research areas to further its usefulness in the creation of biopharmaceuticals. It will be crucial to address these issues if pullulan is to become a flexible and efficient stabilizer in the rapidly changing biologics market.</p>