The dysfunctional islet β-cell triggered by excessive deposition of Zn2+ constituted a striking indicator of the occurrence of diabetic disease. However, it remained a formidable challenge to reflect the real-time function of β-cell by monitoring the Zn2+ content. Herein, multistage photoactivatable Zn2+-responsive nanodevice (denoted as AD2@USD1) was presented for sensing, regulating, and evaluating Zn2+ levels in dysfunctional islet β-cells. The photoactivated signatures on the satellite shell layer of the nanodevices and the internally loaded chelating factors effectively identified and intervened in the real-time concentration of Zn2+, the photothermal feedback component decorated on the inner core permitted the assessment of the post-intervention Zn2+ levels, achieving an integrated intervention and prognostic assessment in response to the abnormal islet β-cell function induced by Zn2+ deposition. In this way, one strategy for sensing and regulating islet β-cell function-oriented to Zn2+ was established. Our study introduced AD2@USD1 as a tool for effectively sensing, adjusting, and assessing the Zn2+ level in islet β-cells with abnormalities, gaining a potential breakthrough in the treatment of diabetes.