Cellular and tissue engineering promises new therapeutic options for people suffering from a wide range of diseases. Differentiation of stem cells is a powerful renewable source of these functional replacement cells and tissues that can be grown in the laboratory. Diabetes is cause by the death or dysfunction of insulin-secreting islets, which are a tissue type found in the pancreas that contain β cells and other endocrine cell types. We have recently developed approaches combining modulating the actin cytoskeleton and signal transduction pathways during differentiation to produce stem cell-derived islets (SC-islets) capable of undergoing glucose-stimulated insulin secretion, their primary function. We have further expanded this approach to make SC-islets from patients with diabetes and used CRISPR-Cas9 to correct their diabetes-causing mutations. Upon transplantation into mice with severe pre-existing diabetes, these SC-islets rapidly restore normoglycemia and can maintain this functional cure for a year. Our hope is that one day this technology can be used to replace unhealthy islets in patients for therapy and provide a better disease-in-a-dish model to discover new drugs to prevent, stop, or reverse diabetes progression.