Type 1 diabetes mellitus (T1DM) is the most common autoimmune chronic disease in young patients. It is caused by the destruction of pancreatic endocrine β-cells that produce insulin in specific areas of the pancreas, known as islets of Langerhans. As a result, the body becomes insulin deficient and hyperglycemic. Complications associated with diabetes are life-threatening and the current standard of care for T1DM consists still of insulin injections. Lifesaving, exogenous insulin replacement is a chronic and costly burden of care for diabetic patients. Alternative therapeutic options have been the focus in these fields. Advances in molecular biology technologies and in microfabrication have enabled promising new therapeutic options. For example, islet transplantation has emerged as an effective treatment to restore the normal regulation of blood glucose in patients with T1DM. However, this technique has been hampered by obstacles, such as limited islet availability, extensive islet apoptosis, and poor islet vascular engraftment. Many of these unsolved issues need to be addressed before a potential cure for T1DM can be a possibility. New technologies like organ-on-a-chip platforms (OoC), multiplexed assessment tools and emergent stem cell approaches promise to enhance therapeutic outcomes. This review will introduce the disorder of type 1 diabetes mellitus, an overview of advances and challenges in the areas of microfluidic devices, monitoring tools, and prominent use of stem cells, and how they can be linked together to create a viable model for the T1DM treatment. Microfluidic devices like OoC platforms can establish a crucial platform for pathophysiological and pharmacological studies as they recreate the pancreatic environment. Stem cell use opens the possibility to hypothetically generate a limitless number of functional pancreatic cells. Additionally, the integration of stem cells into OoC models may allow personalized or patient-specific therapies.