Background: The effects of omega-3 polyunsaturated fatty acids (PUFAs) on cerebral vessels have not been clarified until now. Thus we investigated the efficacy of omega-3 PUFAs supplementation on cerebral blood flow velocity and vascular resistance via transcranial doppler (TCD). Methods: Consecutive twenty patients (13 male and 7 female) with at least 1 cerebrovascular risk factor or a known cerebrovascular disease were enrolled. Patients were treated with omega-3 PUFAs (1 g, two times per day) for 12 weeks. Cerebral blood flow velocity, resistance index, and pulsatile index were checked before and after 12 weeks of treatment using TCD. Results: The change of resistance index in right MCA (from 0.58 ± 0.07 to 0.55 ± 0.07, p = 0.042) and left PCA (from 0.56 ± 0.07 to 0.53 ± 0.06, p = 0.037) showed significant improvement after 12 weeks of omega-3 PUFAs treatment. The changes in other vessels, however, failed to show any significant changes compared to the baseline. Conclusions: Omega-3 PUFAs treatment showed feasible efficacies for cerebral vascular resistances in this open label trial. To confirm these results, larger samples of patients and longer period of follow-up is warranted.