The regulation of islet cell biology is critical for glucose homeostasis. N⁶-methyladenosine (m⁶A) is the most abundant internal messenger RNA (mRNA) modification in mammals. Here, we report that the m⁶A landscape segregates human type 2 diabetes (T2D) islets from controls significantly better than the transcriptome and that m⁶A is vital for β-cell biology. m⁶A sequencing in human T2D islets reveals several hypomethylated transcripts that are involved in cell-cycle progression, insulin secretion, and the insulin/IGF1–AKT–PDX1 pathway. Depletion of m⁶A levels in EndoC-βH1 cells induces cell-cycle arrest and impairs insulin secretion by decreasing AKT phosphorylation and PDX1 protein levels. β-cell-specific Mettl14 knockout mice, which display reduced m⁶A levels, mimic the islet phenotype in human T2D with early diabetes onset and mortality owing to decreased β-cell proliferation and insulin degranulation. Our data underscore the significance of RNA methylation in regulating human β-cell biology, and provide a rationale for potential therapeutic targeting of m⁶A modulators to preserve β-cell survival and function in diabetes.