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Cardiovascular diseases (CVDs) represent the leading global cause of disability and premature mortality, imposing an immense burden on global public health and medical systems. Notwithstanding the availability of multiple clinical drugs, controlling the incidence and mortality of CVDs remains a formidable challenge. Pyroptosis, a specialized pro-inflammatory programmed cell death marked by membrane pore formation, is involved in the pathogenic mechanisms of several CVDs. Phytomedicines, encompassing plant-derived metabolites and multi-botanical botanical formulations, can inhibit pyroptosis by regulating related pathways, thereby exerting cardiovascular protective effects. This review elaborates on the core molecular characteristics, morphological changes, and canonical/non-canonical activation mechanisms of pyroptosis. Systematically delineate the pivotal function of pyroptosis in the pathogenic advancement of predominant CVDs. Additionally, analyze the regulatory impacts and fundamental molecular processes of natural products and multi-botanical botanical formulations on pyroptosis in various CVDs. Collectively, this research positions the manuscript as a systematic preclinical review focused on pyroptosis-targeted natural therapeutic candidates, systematically outlines pyroptosis-mediated pathological cascades in CVDs, and highlights the translational potential of natural agents that block pyroptosis. Nearly all supporting evidence summarized herein remains pre-clinical; well-designed human studies are urgently required before any real-world clinical application can be considered.