SPD suppresses oxidative stress and endoplasmic reticulum stress in vivo and in vitro. Mice and primary neonatal mouse cardiomyocytes were treated with or without SPD and underwent the following detections: (A) DHE staining of myocardial tissue; (B) mRNA expression of GRP94, GRP78, ATF-4 and Chop; (C) Intracellular ROS level detection was determined by fluorescence microscopy; (D) Representative western blot of Prdx-1, TfR-1, p-p38, and p-JNK in cardiomyocytes; (E) The ER-related protein expression of GRP94, GRP78, ATF-4, and Chop was determined by western blot. *P < 0.05 vs Control group; #P < 0.05 vs HG group (n ≥ 3). SPD: Spermidine; DHE: Dihydroethidium; ROS: Reactive oxygen species; ER: Endoplasmic reticulum; HG: High glucose