Cardiovascular diseases pose a major threat to both life expectancy and quality of life worldwide, and a concerning level of disease burden has been attained, particularly in middle- and low-income nations. Several drugs presently in use lead to multiple adverse events. Thus, it is urgently needed to develop safe, affordable, and effective management of cardiovascular diseases. Emerging evidence reveals a positive association between polyphenol consumption and cardioprotection. Whole wheat grain and allied products are good sources of polyphenolic compounds bearing enormous cardioprotective potential. Polyphenolic extract of the entire wheat grain contains different phenolic compounds viz. ferulic acid, caffeic acid, chlorogenic acid, p-coumaric acid, sinapic acid, syringic acid, vanillic acid, apigenin, quercetin, luteolin, etc. which exert cardioprotection by reducing oxidative stress and interfering with different toxicological processes. The antioxidant capacity has been thought to exert the cardioprotective mechanism of wheat grain polyphenolics, which predominantly suppresses oxidative stress, inflammation and fibrosis by downregulating several pathogenic signaling events. However, the combined effect of polyphenolics appears to be more prominent than that of a single molecule, which might be attained due to the synergy resulting in multimodal cardioprotective benefits from multiple phenolics. The current article covers the bioaccessibility and possible effects of wheat-derived polyphenolics in protecting against several cardiovascular disorders. This review discusses the mechanistic pharmacology of individual wheat polyphenols on the cardiovascular system. It also highlights the comparative superiority of polyphenolic extracts over a single phenolic.