Sodium-glucose cotransporter-2 (SGLT2) inhibitors, initially developed for treating type 2 diabetes, have demonstrated significant cardioprotective effects in patients with and without diabetes, particularly in those with heart failure (HF). These inhibitors have also shown potential anticancer properties, making them a promising therapeutic option in cardio-oncology. The review highlights the established cardioprotective effects of SGLT2 inhibitors in HF, including improved cardiac metabolism, reduced oxidative stress, modulation of neurohormonal pathways, attenuation of myocardial inflammation, and preservation of endothelial function. Preclinical and clinical studies support their use in mitigating cardiotoxicity associated with cancer treatments, such as anthracyclines, proteasome inhibitors, and tyrosine kinase inhibitors. Mechanisms of cardioprotection include anti-inflammatory, antioxidant, ER stress mitigation, ketogenesis, enhanced energy metabolism, autophagy, inhibition of ferroptosis, and inhibition of ET-1. Additionally, preclinical studies suggest potential anticancer effects of SGLT2 inhibitors, particularly canagliflozin and dapagliflozin, in various cancer models, including hepatocellular carcinoma, glioblastoma, osteosarcoma, pancreatic cancer, prostate cancer, lung cancer, cervical cancer, renal cancer, papillary thyroid cancer, and colon cancer. These findings highlight the potential of SGLT2 inhibitors as dual-effective agents in cardio-oncology, offering both cardioprotective and anticancer benefits.Sodium-glucose cotransporter-2 (SGLT2) inhibitors, initially developed for treating type 2 diabetes, have demonstrated significant cardioprotective effects in patients with and without diabetes, particularly in those with heart failure (HF). These inhibitors have also shown potential anticancer properties, making them a promising therapeutic option in cardio-oncology. The review highlights the established cardioprotective effects of SGLT2 inhibitors in HF, including improved cardiac metabolism, reduced oxidative stress, modulation of neurohormonal pathways, attenuation of myocardial inflammation, and preservation of endothelial function. Preclinical and clinical studies support their use in mitigating cardiotoxicity associated with cancer treatments, such as anthracyclines, proteasome inhibitors, and tyrosine kinase inhibitors. Mechanisms of cardioprotection include anti-inflammatory, antioxidant, ER stress mitigation, ketogenesis, enhanced energy metabolism, autophagy, inhibition of ferroptosis, and inhibition of ET-1. Additionally, preclinical studies suggest potential anticancer effects of SGLT2 inhibitors, particularly canagliflozin and dapagliflozin, in various cancer models, including hepatocellular carcinoma, glioblastoma, osteosarcoma, pancreatic cancer, prostate cancer, lung cancer, cervical cancer, renal cancer, papillary thyroid cancer, and colon cancer. These findings highlight the potential of SGLT2 inhibitors as dual-effective agents in cardio-oncology, offering both cardioprotective and anticancer benefits.