Older adults with diabetes mellitus require drug treatment considering their frailty, cognitive function, and hypoglycemia. We investigated the association between diabetic pharmacologic therapy and both diabetic complications and frailty across eight diabetes-specific outpatient clinics nationwide. Participants (aged 60-80 years) who had type 2 diabetes and did not require nursing care were included in the study. Basic attributes, patient background, complications, hypoglycemic status, body weight, body composition, blood tests, grip strength, and Kihon Checklist (a frailty index) and self-care scores were obtained. Descriptive statistics, t-test, chi-square test, and regression analyses were employed for evaluation. Overall, 417 participants were included (224 men, 193 women, mean age 70.1 ± 5.4 years, diabetes duration 14.9 ± 10.9 years, body mass index 24.5 ± 3.8, glycated hemoglobin 7.22 ± 0.98%, proportion of individuals with frailty and prefrailty, 19.9% and 41.0%, respectively). All drugs were used more frequently in prefrailty conditions. Each diabetes medication was related to complications, body composition, and frailty, as follows: sulfonylurea (lower hypoglycemia); glinide (severe hypoglycemia, retinopathy, weaker grip strength, high Kihon Checklist score, decreased physical activities); alpha-glucosidase inhibitors (no association); biguanide (high body mass index, high body fat, stronger grip strength); thiazolidinedione (decreased instrumental activities of daily living); dipeptidyl-peptidase-4 inhibitors (no association); sodium-glucose cotransporter 2 inhibitors; retinopathy, high body mass index and Kihon Checklist score, and depressive mood); glucagon-like peptide-1 receptor agonists (high body mass index and body fat and poor nutritional status); and insulin preparations (hypoglycemia, retinopathy, neuropathy, nephropathy, cardiovascular diseases, weaker grip strength, and high Kihon Checklist score and physical inactivity). Some formulations, such as glinide, sodium-glucose cotransporter 2 inhibitors, and insulin, are associated with an increased frequency of frailty, warranting careful and individualized diabetes treatment.