Aim To evaluate systematically the efficacy of ω-3 polyunsaturated fatty acid supplement in the prevention and treatment of arteriosclerosis. Methods Chinese and foreign language databases from their establishment date to August 14th 2017 were systematically searched for adult human clinical trials to investigate the effects of ω-3 polyunsaturated fatty acid supplements on arteriosclerosis. Experimental study of oral ω-3 polyunsaturated fatty acid supplement and placebo were included in the prevention and treatment of arteriosclerosis. No limits were set on dosage sizes or sample characteristics. The research quality and data were evaluated and cross checked by two researchers independently. Meta analysis was carried out using RevMan 5.3 software. Results 12 studies involving 1325 people were included, including 10 parallel tests and 2 cross tests. The Meta analysis showed that the oral ω-3 polyunsaturated fatty acid supplements could reduce the brachial-ankle pulse wave velocity and the C-reactive protein compared with placebo, and the differences were statistically significant (P＜0.05). However, the effects of oral ω-3 polyunsaturated fatty acid supplement on interleukin-6, adiponectin and leptin were not significant, and the differences were not statistically significant (P＞0.05). Conclusion Oral ω-3 polyunsaturated fatty acid supplements may have the efficacy of reducing the degree of arteriosclerosis and improving the inflammatory response in large and middle arteries.