Type 2 diabetes (T2D) arises from complex interactions between genetic predisposition and environmental influences. Although genome-wide association studies have identified hundreds of risk loci, these variants explain only a small fraction of disease heritability, pointing to additional regulatory mechanisms underlying disease progression. Increasing evidence highlights the epigenome as a critical integrator of environmental cues that shape chromatin accessibility and transcriptional programs, particularly in pancreatic islets. In this talk, I will present our work investigating chromatin remodeling as a key driver of β-cell dysfunction in T2D. Through integrated multi-omics analyses and functional genomic screening, we identify BAF60a, a regulatory subunit of the SWI/SNF chromatin remodeling complex, as a central regulator of islet chromatin dynamics. BAF60a orchestrates β-cell–specific transcriptional networks essential for glucose sensing and insulin secretion. In parallel, our recent studies reveal that BAF60c, another BAF60 family member, plays a critical role in shaping the islet immune microenvironment and maintaining β-cell function through β-cell–macrophage crosstalk. Together, these findings uncover a previously unrecognized epigenetic mechanism contributing to β-cell failure and highlight chromatin remodeling factors as promising targets for precision therapies in T2D.