BACKGROUND: Evidence suggests that bioactive peptides reduce hypertension and affect certain metabolic pathways. METHODS: Fifty-four volunteers with stage 1 prehypertension and/or hypercholesterolemia and/or basal glucose >100 mg/dL were recruited and randomized to pork dry-cured ham (n = 35) or cooked ham (placebo group; n = 19) for 28 days. After a wash-out period, meat products were changed for 28 additional days. Bioactive peptides composition and enzyme inhibitory activities of both products were characterized. Treatment comparisons for the main effects were made using a two (treatment) × two (times) repeated measures minus the effect of cooked ham (placebo). RESULTS: 24 h mean systolic and diastolic pressures decreased up to 2.4 mmHg in the dry-cured ham period (treatment effect, p = 0.0382 y p = 0.0233, respectively) as well as the number of systolic pressure measures > 135 mmHg (treatment effect, p = 0.0070). Total cholesterol levels also decreased significantly after dry-cured ham intake (p = 0.049). No significant differences were observed between the two treatments for basal glucose, HOMA-IR index and insulin levels (p > 0.05). However, a significant rise of ghrelin levels was observed (treatment effect, p = 0.0350), while leptin plasma values slightly decreased (treatment effect, p = 0.0628). CONCLUSIONS: This study suggested the beneficial effects of regular dry-cured ham consumption on the improvement of systolic/diastolic blood pressures and facilitated the maintenance of metabolic pathways, which may be beneficial in the primary prevention of cardiovascular disease.