Exendin-4 (Ex-4) is a promising therapeutic peptide for the clinical treatment of type 2 diabetes, but its instability and immunogenicity result in a short circulating half-life and low bioavailability, which severely limit its clinical application. Here, complex micelles with 4-carboxy-3-fluorophenylboronic acid (FPBA)-modified and positively charged hydrophobic domains on the surface were devised as nanochaperones to mediate the delivery of Ex-4. The nanochaperones can bind Ex-4 on the surface via the synergy of electrostatic and hydrophobic interactions, leading to efficient loading and stabilization of Ex-4. More importantly, the immunogenic site of Ex-4 was shielded by the nanochaperones, thereby effectively reducing the immune clearance and prolonging the half-life. Hyperglycemia-triggered release of Ex-4 was achieved by the hydrophobic to the hydrophilic transformation of the FPBA-modified domains and the introduced negative charge because of the binding of glucose by FPBA. The Ex-4-loaded nanochaperones exhibited an enhanced therapeutic effect on type 2 diabetic mice.