The co-existence of complications and diabetes mellitus is related to a worsening in quality of life compared to not presenting comorbidities. This study aimed to investigate whether there is a different impact on quality of life according to gender and to establish the physiological parameters that these patients have in relation to diabetes-related complications. The sampling was continuous non-probabilistic, involving legal age patients with diabetes mellitus. All of the participants were administered the generic SF-36 quality of life questionnaire. The presence of peripheral artery disease was considered from an ankle brachial index <0.9 and grade II to grade IV of the Leriche–Fontaine classification. Nerve dysfunction was detected from a neurotensiometer test, and the presence of diabetic foot was detected from a dermal examination and co-existence with arteriopathy and/or neuropathy. Men presented significantly better quality of life values on the mental health, emotional role and health transition scales. Despite this, in the presence of complications such as vasculopathy, neuropathy or diabetic foot, the perception of well-being changes, showing that men and women face the disease in different ways. Despite the fact that the physical parameters of diabetic patients are similar according to the complications that they present, the adult women in our environment have lower levels of quality of life than men in most cases. This may be related not only to pathophysiological differences but also to sociocultural factors.