Pancreatic diseases, typically including pancreatic cancer, pancreatitis, and diabetes, pose enormous threats to people's lives and health. To date, therapeutics with high therapeutic efficacy and low side effects are still challenging. With the development of nanotechnology, nanomaterials have successfully been applied in pancretic disease treatment. Here, we first introduce the diversity of nanomaterials and the effects of their different physicochemical properties on pancreatic function. Following this, we analyze the potential of nanomaterials to enhance pancreatic targeting by overcoming the challenges of traditional delivery methods through surface modifications, structural adjustments, and optimized drug loading. Then, we introduce the application of structurally optimized nanomaterials to pancreatic-related diseases. For instance, on pancreatic cancer (as drug delivery platforms, for the promotion of radiation therapy, and as multifunctional tools), pancreatitis (as drug delivery systems, anti-inflammatory and anti-fibrotic agents), and diabetes (as insulin delivery carriers, for protecting pancreatic β cells, and for improving insulin resistance). Through analysis of the progress of current research, we summarize how nanomaterials can enhance treatment efficacy while minimizing side effects. Finally, we look forward to the prospects of nanomaterials in pancreatic disease treatment.