Abstract In this study we evaluated the short-term oral antihypertensive effect of several peptide sequences isolated from cuttlefish (Sepia officinalis) muscle proteins hydrolysates, previously characterized as in vitro angiotensin-I-converting enzyme-inhibitors, in spontaneously hypertensive rats (SHR). Systolic blood pressure (SBP) and the diastolic blood pressure (DBP) of the rats were measured by the tail cuff method before administration and also 2, 4, 6, 8 and 24h post-administration. The peptide sequences Val-Tyr-Ala-Pro, Val-Ile-Ile-Phe and Ala-His-Ser-Tyr showed a clear decrease in SBP and DBP in SHR. Met-Ala-Trp caused a significant decrease of the SBP in the SHR, but this sequence caused a slight decrease in DBP in these animals. SBP and DBP returned to baseline values 24h post-administration of all peptides. Thus, these peptides are bioactive ingredients with potential benefit in the prevention and treatment of hypertension.