The purposes of this study were to compare the effectiveness of monotherapy and combination of oral antidiabetic drugs for lowering blood sugar level. We also would like to perform retrospective study on proper drug selection according to the standards of medical care in diabetes. One hundred fourty-nine diabetic patients with chronic kidney disease who received oral antidiabetic therapy at Phramongkutklao Hospital between 1st Jan 2015 and 31st Dec 2017 were retrospectively analyzed. Patients above 18 years old and taken oral antidiabetic drugs for at least 3 months were enrolled in this study. Blood glucose levels were collected twice which have at least 3 months spacing. Statistical analysis was carried out using IBM SPSS Statistics version 22. The results showed that using metformin or sulfonylureas as a monotherapy significantly reduced A1C level at p-value 0.01 while using 2 classes of antidiabetic drugs which are sulfonylureas with thiazolidinediones or metformin were significantly reduced A1C level at p-value 0.05. In addition, using more than 2 classes of antidiabetic drugs, metformin plus sulfonylureas together with thiazolidinediones, can reduce A1C level significantly (p<0.05). Furthermore, this research also found that metformin can increase serum creatinine level and eGFR significantly (p<0.05) compared to the levels before drug treatment. Base on the findings