Diabetic foot foot ulcer (DFU) is a serious complication of diabetes mellitus, and possibly the major morbidity of the diabetic foot. It is the most common foot injury in diabetic patients and can lead to lower-extremity amputation. Management of DFU requires a systematic knowledge of the major risk factors for amputation, frequent routine evaluation, scrupulous preventive maintenance, and correction of peripheral arterial insufficiency. Carboxytherapy refers to the subcutaneous injection of CO2 to improve the microcirculation and promote wound healing by stimulating the microcirculation. Since optimal ulcer healing requires adequate tissue perfusion, it is considered that carboxytherapy could be useful in the treatment of DFU. The present prospective clinical study included 40 patients with different sizes and types of chronic DFU. In addition to cleaning of the wound, antibiotics, and debridement as necessary, the treatment protocol included blood sugar control, medication, healthy habits, no weight-bearing, and carboxytherapy. The results showed that this treatment which included carboxytherapy promoted wound healing and prevented amputation. These positive effects should be confirmed through a complete study that includes different clinical and instrumental parameters.