Peroxisomes are still enigmatic organelles six decades after their discovery. Their importance for pancreatic β-cell function remains largely unexplored. Baboota, Shinde, and colleagues assessed the abundance of peroxisomes in the endocrine pancreas and used an in vivo loss-of-function approach to investigate the role of peroxisomes in pancreatic β-cells. They provide evidence that peroxisomal metabolism plays an essential role in the preservation of β-cell integrity. This suggests that enhancing peroxisome activity is a potential avenue to support β-cell function in metabolic stress conditions.