N6-methyladenosine (m6A) mRNA methylation has been shown to regulate obesity and type 2 diabetes. However, whether METTL3, the key methyltransferase for m6A mRNA methylation, regulates β-cell failure in diabetes has not been fully explored. Here, we show that METTL3 is downregulated under the inflammatory and oxidative stress conditions, and islet β-cell-specific deletion of Mettl3 induces β-cell failure and hyperglycemia, which is likely due to decreased m6A modification and reduced expression of insulin secretion-related genes. Overall, METTL3 might be a potential drug target for the treatment of β-cell failure in diabetes.