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Cardiovascular diseases (CVDs) remain a major global health challenge, underscoring the need for novel, accessible, and effective therapeutic strategies. This review critically evaluates the phytochemical composition and cardioprotective potential of Passiflora species, summarizes the mechanisms of action of their principal bioactive compounds, and identifies key research gaps hindering clinical translation. With over 500 species distributed worldwide, many Passiflora plants are traditionally used in herbal medicine. Preclinical evidence suggests that compounds such as phenolics, alkaloids, and triterpenoid saponins exert cardioprotective effects through antioxidant and anti-inflammatory activities, vasodilation, blood pressure regulation, endothelial function improvement, and autonomic nervous system modulation. However, these findings are largely based on a limited number of species, often using non-standardized extracts, and lack comprehensive structure-activity relationship (SAR) analyses and clinical validation. Endemic Passiflora species remain underexplored, despite their potential to yield novel compounds with enhanced bioactivity. This review emphasizes the need for extract standardization, robust pharmacokinetic studies, and the integration of omics technologies and molecular modeling to accelerate compound discovery and development. Overall, Passiflora species contain promising bioactive molecules with significant in vitro and in vivo cardioprotective effects. Nonetheless, rigorous and standardized research, including clinical trials, is essential to fully assess their therapeutic value and support their integration into evidence-based cardiovascular care.