The prevalence of Diabetes Mellitus (DM) is estimated to be about 300 million people worldwide. Poor diabetes control may lead to complications such as diabetic foot ulcers or amputations. The high incidence of amputation is still considered as an important socio-economic problem. The increased incidence of diabetes increases the incidence of diabetic foot ulcers. Patients with diabetic foot ulcers may also be at high risks of mortality due to the associated cardiovascular diseases. Foot ulcers are one of the most important chronic complications of diabetes and are regarded as a major problem which significantly affects the quality of life. Diabetic foot ulcers is also the most important cause of morbidity and mortality in DM patients and is considered a major psychological, economical, and social problem which has been resulted in the hospitalization of patients with DM all around the world. The aim of this study is to evaluate the effectiveness of ozone therapy (as a complementary treatment) through different techniques in the management of diabetic foot ulcers. The present study provides clinical evidence which supports and recommends the benefits of ozone therapy in diabetic foot ulcer.