Background: The Indian plant root Salacia reticulata, which is rich in alpha-glucosidase inhibitors, is used for metabolic disorders in Ayurvedic medicine. Vitamin D₃ is also used in the treatment of some metabolic diseases. Our goal was to determine its potential effect for humans with obesity. Material: In a randomized open-label study, we investigated 40 healthy participants aged 30 - 60 years, physically active, with a body mass index (BMI) of 25 - 45. The participants were randomly allocated into two groups. Body weight, BMI, and body composition were measured. Both groups (A and B) received a guideline for lifestyle and fitness training for 4 weeks. Group B additionally took one capsule containing 200 mg of Salacia reticulata and 1.6 µg (i. e. 64 IU) Vitamin D₃ (SRD) 3 times/day with the meals. Results: Significant weight and body-fat reduction within 4 weeks was observed. Group A lost 1.8 kg or 2.1 %, group B lost 5.3 kg or 6.1 % (p = 0.03), therefore BMI reduction was achieved. While Group A lost 1.4 % of body fat, group B reduced it by 4.5 % (p = 0.01). Conclusion: These promising results suggest that the combination of Salacia reticulata and Vitamin D₃ might be highly valuable and potent to treat overweight and obesity, especially in addition to a modifying lifestyle program. Further research is needed in addition to this study to clarify pathways and effect mechanisms.