Smoking and diabetes mellitus (DM) have been identified as 2 major cardiovascular risk factors for many years. In the field of cardiovascular diseases, considering sex differences, or gender differences, or both has become an essential element in moving toward equitable and quality health care. We reviewed the effect of sex or gender on the link between smoking and DM. The risk of type 2 DM due to smoking has been established in both sexes at the same level. As is the case in the general population, the prevalence of smoking in those with DM is higher in men than in women, although the decrease in smoking observed in recent years is more pronounced in men than in women. Regarding chronic DM complications, smoking is an independent risk factor for all-cause mortality, as well as macrovascular and microvascular complications, in both sexes. Nevertheless, in type 2 DM, the burden of smoking appears to be greater in women than in men for coronary heart disease morbidity, with women having a 50% greater risk of fatal coronary event. Women are more dependent to nicotine, cumulate psychosocial barriers to quitting smoking, and are more likely to gain weight, which might make it more difficult for them to quit smoking. Smoking cessation advice and treatments should take into account gender differences to improve the success and long-term maintenance of abstinence in people with and without DM. This might include interventions that address emotions and stress in women or designed to reach specific populations of men.