The aim of this updated systematic review is to summarize the evidence of the effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) on non-communicable diseases (NCDs). Publications of meta-analysis up to August 2014 were systematically searched from PubMed, the Cochrane and EMBASE databases. N-3 PUFAs have the following beneficial effects; cardio-protective effects, reduce ischemic stroke risk in both men and women and total stroke risk in women, increase insulin sensitivity in Asians, decrease risk of breast cancer and colorectal cancer in men. However, n-3 PUFAs may have unfavourable effects on type 2 diabetes in Caucasians. In conclusion, n-3 PUFA plays a crucial role in the prevention of NCDs, however, unfavourable effects should be considered in subjects with certain clinical conditions. Cross-cultural studies on the effect of n-3 PUFA on type 2 diabetes are needed to verify why diabetic patients with different ancestries have a different response to n-3 PUFA.