Massive changes have occurred in our diet. A growing consumption of vegetal oils rich in omega-6 (ω-6) and a depletion of omega-3 (ω-3) fatty acids (FAs) in our food has led to an imbalance between ω-3 and ω-6. In particular, eicosapentaenoic (EPA)/arachidonic acid (AA) ratio seems to be an indicator of this derangement, whose reduction is associated to the development of metabolic diseases, such as diabetes mellitus. Our aim was therefore to investigate the literature on the effects of ω-3 and ω-6 FAs on glucose metabolism. We discussed emerging evidence from pre-clinical studies and from clinical trials. Notably, conflicting results emerged. Source of ω-3, sample size, ethnicity, study duration and food cooking method may be responsible for the lack of univocal results. High EPA/AA ratio seems to be a promising indicator of better glycemic control and reduced inflammation. On the other hand, linoleic acid (LA) appears to be also associated to a minor incidence of type 2 diabetes mellitus, although it is still not clear if the outcome is related to a reduced production of AA or to its intrinsic effect. More data derived from multicenter, prospective randomized clinical trials are needed.