The interface between metabolic disorders and heart disease is an active area of research, with diabetes, metabolic syndrome, ageing, and obesity recognised as significant risk factors for impaired cardiac function. Metabolic agents such as metformin, myo-inositol and berberine have traditionally been prescribed or otherwise utilised for improving insulin sensitivity and glucose homeostasis. Epidemiological data and early clinical trials suggest cardiovascular-related benefits of these compounds in the respective populations, but little is known about their effects on cardiac cells. We therefore set out to characterise the direct impact on cardiomyocytes beyond obvious benefits to systemic health. As aberrant metabolism and oxidative stress play a major role in the development and progression of these interrelated pathologies, a specific focus was placed on changes in the redox landscape. Using state-of-the-art mass spectrometry and preservative two-step cysteine alkylation, proteomic and redox-proteomic characterisation of these compounds was performed in AC16 human cardiomyocytes. Complementary glutathione status was assessed as a cellular marker of oxidative stress. Initial observations, particular to antioxidative capacity, were further explored in an ischaemia-reperfusion injury model employing hiPSC-derived cardiac organoids, providing additional clinical and in vivo context. Here we provide a comprehensive depiction of the cardiac proteome and redox state following treatment with commonly applied metabolic agents at pharmacologically and clinically relevant concentrations. Notably, we show the impact of myo-inositol on redox-sensitive active sites of PKM and FASN, key regulators of cellular metabolism that were previously identified in the tissue of failing hearts. Additional validation in a model of reperfusion injury highlights the potential cardioprotective effects by preserving metabolic capacity and mediating the stress response to ensure continued cellular function. These findings provide a solid foundation for future investigations into clinical applications.