Arterial stiffness and hemodynamics may be increased following a bout of resistance exercise. Oral creatine supplementation (Cr) may attenuate cardiovascular responses after exercise via improved anaerobic metabolism. This study was aimed to determine the effect of Cr on hemodynamic and arterial stiffness responses after acute isokinetic exercise. Sixteen healthy males (22.6 ± 0.6 year) were randomly assigned to either placebo (Pl, n = 8) or Cr (n = 8) (2 × 5 g/day) for 3 weeks. Brachial systolic blood pressure (SBP), heart rate (HR), brachial-ankle pulse wave velocity (baPWV), and leg PWV were measured in the supine position at rest before and after the interventions. After the supplementation period, parameters were also measured 5 min (PE5) and 15 min (PE15) after two sets of leg isokinetic exercise. There was no difference between the groups in resting measurements before and after the supplementation. Compared with the Pl group, the Cr group had attenuated (P < 0.05) increases in SBP at PE5 (Pl 14.0 ± 2.5, Cr 5.6 ± 2.3 mmHg), HR at both P5 (Pl 28 ± 4 vs. Cr 16 ± 2 beats/min) and PE15 (Pl 21 ± 3, Cr 11 ± 2 beats/min) and rate pressure product at P5 (Pl 45.8 ± 6.4, Cr 24.8 ± 2.2) and P15 (Pl 34.2 ± 5.0, Cr 15.9 ± 6.0). Compared with the Pl group, the Cr group had suppressed increases in baPWV at PE5 (Pl 1.5 ± 0.4, Cr -0.1 ± 0.4 m/s) and PE15 (Pl 1.1 ± 0.2, Cr -0.3 ± 0.3 m/s) and returned SBP to pre-exercise values at PE15 (Pl 10.6 ± 2.8, Cr 2.1 ± 2.6 mmHg). PWV in the exercised leg decreased at PE5 in both groups. These findings suggest that Cr supplementation attenuates the hemodynamic and baPWV responses after acute isokinetic exercise.