Introduction: Obesity is a known risk factor for type 2 diabetes mellitus (T2DM), and weight-loss seems prudential in T2DM risk reduction. In the current study, we evaluated the efficacy of a short-term yoga-based lifestyle intervention in weight-loss, and assessed its impact on interleukin (IL)-6, vitamin D, fasting plasma glucose (FPG), insulin resistance, waist/hip ratio, lipid profile, and blood pressure in overweight/obese subjects vs. apparently healthy normal weight control subjects. Methods: A total of 68 subjects were enrolled in this study, of which 34 were overweight/obese (BMI ≥23 to <35 kg/m2 per Asian cut-off values) and 34 were apparently healthy normal-weight control subjects. The study was conducted in two phases. In Phase I, all the 68 subjects attended a 10 day directly supervised yoga-based lifestyle intervention program, which was hospital-based. End of Phase I was end-of-study for normal weight subjects while overweight/obese subjects entered Phase II, and continued the intervention while home-based till Day 30. Weight-loss and diabetes risk factors were assessed at Baseline, Day 10 (for both the study groups) and Day 30 (for overweight/obese subjects). Results: In overweight/obese subjects, there was a significant reduction from Baseline to Day 10 in weight (73.20±10.00 vs. 72.35±9.78 kg, p=0.0001), BMI (26.49±3.67 vs. 26.26±3.65 kg/m2, p=0.004), waist/hip ratio (0.91±0.10 vs. 0.90±0.09, p=0.043), FPG (p=0.005), and a significant improvement in lipid profile (p<0.05). Also in this group, there was a significant reduction in median fasting insulin (8.50 vs. 8.30 μIU/dL, p=0.049), insulin resistance (HOMA-IR; 2.55 vs. 1.53, p=0.018), and levels of IL-6 (1.16 vs. 1.11 pg/mL, p=0.031). At Day 30, weight-loss was sustained, and systolic blood pressure was also decreased (p=0.017). The correlation analysis showed that IL-6 decreased with a decrease in waist/hip ratio. Also, serum 25-OH-vitamin D increased with a decrease in weight, FPG, and increased with increase in HDL. There were no notable changes in the control group. Conclusions: This short-term lifestyle intervention resulted in a significant weight-loss even in a short duration, as early as 10 days. This reduction in weight resulted in a reduction in diabetes risk factors in overweight/obese subjects.