Introduction: Diabetes mellitus (DM) is a metabolic disorder characterized by abnormal carbohydrate, fat, and protein metabolism, which is clinically diagnosed based on hyperglycemia. Ayurveda has explained Avyayama (lack of exercise) as the first and foremost cause for diabetes. Objectives: The main aim of the study was to assess the safety and clinical efficacy of Nisha Katakadi Kashaya and Yashada Bhasma (single as well as in combination) in the management of Type 2 Diabetes Mellitus. Materials and Methods: This study was an interventional, randomized, openlabel multi-center clinical study. Total 193 subjects were treated with Nisha Katakadi Kashaya, 15 ml, Capsule Yashada Bhasma 125 mg individually in 1st and 2nd groups and Nisha Katakadi Kashaya, 15 ml and capsule. Yashada bhasma, 125 mg as a combination in the 3rd group. The duration of treatment was 12 weeks (84 days) in all the groups and the effect of the drug was assessed up to 14th week. Results: The effect of treatment was observed statistically highly significant (< 0.001) in relieving subjective parameters diabetes symptoms questionnaire (DSQ) score) and improving the quality of life of the subjects assessed by SF-36 (RAND) health survey score. But there is no change observed in parameters, i.e. HbA1c and Blood sugar levels. Conclusion: Ayurveda treats Madhumeha in a broad concept which does not include just the hyperglycemia; the study provides good evidence in support of the efficacy and safety of the trial drugs individually and in combination in response to subjective parameters. It is also observed that, all the safety parameters like liver function test (LFT), kidney function test (KFT) and renal parameters also remain within normal limits.