Environmental toxins such as heavy metals, industrial pollutants, pesticides, and environmental chemicals are becoming recognized as key contributors to cardiotoxicity, with considerable implications for worldwide cardiovascular health. Humans are unintentionally exposed to environmental toxins, which have a variety of cardiopathologic effects. These poisons cause oxidative stress, inflammation, mitochondrial dysfunction, and dysregulation of important physiological pathways which ultimately contribute to cardiac dysfunction and diseases. Natural compounds originating from medicinal plants, microbes, and marine organisms have emerged as promising cardioprotective agents. These bioactive chemicals exhibit potent anti-oxidant, anti-inflammatory, and cardio-regenerative activities, which target molecular mechanisms involved in cardiotoxicity. Phytochemicals such as terpenoids, polyphenols, flavonoids, and alkaloids, as well as bioactive peptides and microbial metabolites, have shown promise in pre-clinical and clinical investigations for preventing toxin-induced cardiac damage. Therefore, this review highlights the mechanisms of environmental toxin-induced cardiotoxicity and the novel therapeutic agents for the prevention and treatment of environmental toxin-induced cardiotoxicity.