Overproduction of reactive oxygen species (ROS) is a key determinant of cardiac contractile dysfunction in diabetic cardiomyopathy, whereby cellular ROS directly reduce endogenous antioxidant capacity. Current preclinical evidence suggests that dietary antioxidant therapies can scavenge ROS and mitigate ROS-mediated alterations, thereby limiting contractile dysfunction by restoring redox balance. While cysteine-containing proteins are thought to be the cellular targets of excess ROS, the specific protein targets and networks remain to be defined. We aimed to identify redox-modified peptides in diabetic cardiomyopathy to identify potential sites that, if protected by acute or chronic antioxidant interventions, could improve functional outcomes by rescuing redox-susceptible systems. We utilised a low-dose streptozotocin (STZ) and high-fat diet (HFD) to induce diabetic cardiomyopathy within 8-weeks. Further groups were supplemented with either vitamin-A (8000IU/kg), -C (1000mg/kg), -E (0.84g/kg), creatine (2%), or phytoestrogen (200mg/kg) to the HFD to provide chronic antioxidant protection. Animal biometrics were monitored across the 8-week period, including body weight, percentage adiposity, and blood glucose. All supplements showed a significant reduction in the degree of adiposity, despite similar average weight gain with regular HFD. Global strain analysis by echocardiography measured in vivo contractility, showing that some interventions improved left ventricular function. After the 8-week protocol, hearts are then excised for Langendorff isolated ex vivo perfusion for 5-minutes. Two separate groups were perfused for the same duration (5 minutes) with either N-propionylglycine (MPG; 1mM) or N-acetylcysteine (0.4mM), to provide acute antioxidant protection. Ventricular tissue was prepared for paired proteomics and metabolic analysis using DIA-MS/MS proteomics and targeted metabolomics via MS/MS. Both acute and chronic exogenous antioxidants salvaged endogenous antioxidant systems and contractile proteins, but metabolic systems were redox-modified, with distinct profiles between acute and chronic interventions. Within the chronic dietary treatments, similarities were observed among vitamins A, C, and E, with creatine and phytoestrogen providing similar responses. Thus, each antioxidant may not hold equal protective capabilities in restoring contraction in diabetic cardiomyopathy.