Several epidemiological studies have elucidated that consumption of foods rich in anthocyanins decreases the risk of cardiovascular disease (CVD). Therefore, the first objective of this study was to systematically review randomized controlled trials (RCTs) assessing the effects of purified anthocyanin mixtures and anthocyanin-rich extracts on CVD risk factors. The findings of this systematic review show that purified anthocyanin mixtures may have positive effects on certain markers of CVD; however, there is limited evidence surrounding the potential of purified anthocyanin mixtures in subjects with hypertension. Therefore, our second objective was to investigate the effects of the purified anthocyanin (cyanidin-3-O-glucoside, C3G) in vitro in adult rat cardiomyocytes and cardiac fibroblasts (CF) exposed to endothelin 1 (ET1), and in vivo in spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKY) alone or combination (10 mg/kg/day each) with the diuretic (hydrochlorothiazide, HCT). C3G prevented ET1-induced cardiomyocyte death and hypertrophy and reduced CF activation. HCT slowed the rise of blood pressure in SHRs over time, but C3G had no effect on blood pressure. SHRs treated with C3G, HCT, and C3G+HCT had lower left ventricular mass and shorter isovolumetric relaxation time compared to control SHRs. We next focused on characterizing the immune system dysfunction and investigating whether C3G and HCT can affect T-cell dysfunction in SHRs. Splenocytes of SHRs produced lower concentrations of cytokines ex vivo in response to concanavalin A stimulation, compared to WKY rats. While there was no effect of C3G on cytokine production in both WKY rats and SHRs, HCT treatment significantly decreased cytokine production in SHRs. SHRs had a lower proportion of regulatory T-cells (Tregs) compared to WKY rats with no effect of C3G or HCT. In conclusion, C3G may have the potential to mitigate cardiac abnormalities in SHRs independently of any effects on blood pressure. The observed cardioprotective effects of C3G and HCT are not mediated through Tregs. Future studies are needed to explore the potential of C3G in subjects with established hypertension and to identify the mechanisms underlying its cardioprotective effects observed in this study.