The present study revealed several major findings: (1) HKL protected rat hearts (in vivo) and H9c2 cells (in vitro) against I/R injury in the T1D state; (2) HKL effectively reduced I/R injury-induced oxidative stress and apoptosis in T1D; and (3) the cardioprotective effects of HKL were mediated, at least in part, by activating the SIRT1-Nrf2 signaling pathway. This evidence concerns the gene NFE2L2 and type 1 diabetes mellitus.