Background and aims: The aims of the present study were to evaluate the effectiveness of Hydroxychloroquine as an add-on therapy to metformin and Sulfonylurea (SU) in reducing glycosylated hemoglobin (HbA1c) to achieve therapeutic goals. Methods: In this open-labelled comparative observational study, two groups of 100 uncontrolled Type 2 Diabetes Mellitus (T2DM) patients in each were studied for 24 Weeks (6 months). Both the groups were divided into patients who were on triple drug combinations. One group receiving Metformin,Glimepiride and Tenelegliptin and the other group received Metformin,Glimepiride and Hydroxychloroquine. In each group fasting blood sugar and as postprandial blood sugar were tested at the start of the study and at 4 weeks intervals. HbA1c was tested at the beginning of study, at 12 Weeks (3 months) and at the end of 24 weeks (6 months). Results: After 24 weeks of treatment, there was significant fall in fasting, as well as postprandial blood sugar and HbA1c levels in patients containing Hydroxychloroquinine in comparison to Tenelegliptin. Conclusions: Hydroxychloroquine significantly improves glycaemic control in patients with T2DM when prescribed as an add-on therapy in addition to two other commonly prescribed antidiabetic drugs such as Glimipirde and metformin combination, and even its efficacy to reduce blood sugar is compairable to newer generation drugs like Teneligliptin. Hydroxychloroquine may be considering as an ideal add-on third drug therapy in the treatment of uncontrolled T2 DM patients.