Introduction Diet is a cornerstone of comprehensive treatment of diabetes mellitus. The macrobiotic diet is low in fat and rich in dietary fiber, vegetables and whole grains, and therefore may be a good therapeutic option. Objective Assess the influence of the Ma-Pi 2 macrobiotic diet on physical, hematologic and biochemical variables, as well as on hypoglycemic medication, in adults with type 2 diabetes mellitus. Materials and Methods A 6-month dietary intervention was carried out in 16 adults with type 2 diabetes mellitus and poor glucide metabolism control (glycosylated hemoglobin, HbA1 >8.5%) receiving treatment at the Diabetic Care Center in Colón, Matanzas province, Cuba. The diet was prepared and served daily by macrobiotic specialists. Type and amount of food consumed and nutritional content were assessed using a weighted food-consumption survey. At onset and termination of the intervention, anthropometric and body composition variables were measured, as were biochemical (glucide and lipid metabolism) and other nutritional safety variables, and hypoglycemic drug use. Results The diet provided sufficient energy and protein. It was low in fat, high in complex carbohydrates and dietary fiber, and provided adequate amounts of vitamins and minerals, except for vitamin B12. At 6 months, anthropometric variables were significantly lower, lean body mass was preserved, and glucide and lipid metabolism was controlled. All participants were able to eliminate insulin treatment, and 25% continued treatment with glibenclamide only. Mean total cholesterol, LDL cholesterol and triglyceride values dropped 16.4%, 22.7% and 37.0%, respectively, while mean HDL cholesterol rose 97.8%. Mean glycemia and HbA1 values also decreased 63.8% and 54.5%, respectively. According to lipid levels and ratios, cardiovascular risk was also considerably reduced. Hemoglobin, total protein, albumin and creatinin levels indicated that nutritional safety was maintained. There were no adverse events. Conclusions In the 6-month intervention, the Ma-Pi 2 macrobiotic diet had a positive influence on weight control, body fat, and glucide and lipid metabolism in patients with type 2 diabetes mellitus. Further research is needed to validate these encouraging results, particularly a clinical trial in which a control group receives the standard diet recommended for diabetic patients.