Cardiovascular diseases remain the leading cause of death globally, with elevated blood pressure identified as a major regulating risk factor. Cannabidiol, a non-intoxicating compound from Cannabis sativa L., Cannabaceae, has established cardioprotective effects in preclinical studies through antioxidant, anti-inflammatory, and vasodilatory mechanisms. This systematic review and meta-analysis assessed the effects of cannabidiol on systolic and diastolic blood pressure in humans. A comprehensive search in PubMed, Cochrane Library, Scopus, and Embase databases up to May 2024 identified four randomized controlled trials comprising 104 participants, three assessing short-term administration and one chronic use in hypertensive individuals. Meta-analysis demonstrated a significant reduction in systolic blood pressure after acute cannabidiol intake (SMD –1.06; 95%CI –2.01 to –0.11; p = 0.03), but no significant change in diastolic blood pressure (SMD –1.17; 95%CI –2.55 to 0.20; p = 0.09). Chronic administration promoted reductions of 7.01 mmHg in systolic and 4.55 mmHg in diastolic blood pressure. Despite promising trends, the small number of trials, limited sample sizes, and substantial heterogeneity reduced the overall certainty of the evidence. These findings suggest that cannabidiol may benefit blood pressure control, specifically with prolonged use in hypertensive patients, but further high-quality randomized controlled trials are required to approve its efficacy, safety, and clinical applicability in cardiovascular care. Graphical Abstract