Phytochemicals have garnered significant attention for their potential cardioprotective effects against myocardial oxidative stress and damage, owing to their antioxidant and anti-inflammatory properties. Compounds from various classes, including polyphenols, terpenes, alkaloids, and quinones, have been well documented. Among them, resveratrol, curcumin, berberine, and cryptotanshinone have demonstrated benefits in cardiovascular diseases and anticancer drug-induced cardiotoxicity. Collectively, these phytochemicals reduce myocardial oxidative stress and reactive oxygen species by scavenging free radicals, upregulating antioxidant enzyme activity, stabilizing mitochondrial membranes, and inhibiting inflammatory signaling pathways. In this chapter, we discuss several classes of phytochemicals, their chemical properties, and molecular targets of biological action. Subsequently, we describe their mechanisms of cardioprotection from studies in vitro and in vivo as well as clinical trials. As phytochemicals are derived from natural sources, mostly plants, they represent cost-effective methods and have fewer side effects as compared to the synthetic drugs.