Introduction: Obesity is a condition of abnormal or excessive fatness, and dyslipidemia is a condition with abnormal raised levels of any one or all lipids in the blood. Ayurveda compares signs and symptoms of obesity and dyslipidemia with the disease Sthaulya/Medoroga. Vyoshadi Guggulu and Haritaki Churna are the most commonly used medicines in the management of Sthaulya. However, the safety of these drugs was not evaluated until now through clinical trials. Objective: The objective of this study was to assess clinical safety of Vyoshadi Guggulu and Haritaki Churna in the management of obesity (Sthaulya) and dyslipidemia. Materials and methods: A prospective, open-label multicentric study was carried out at peripheral institutes of the Central Council for Research in Ayurvedic Sciences (CCRAS). Total 306 patients satisfying selection criteria were randomly selected from the outpatient department of respective centers and were administered Vyoshadi Guggulu (3 tablets of 500 mg) and Haritaki Churana (3 gm twice daily) in case of obesity, and Vyoshadi Guggulu (2 tablets of 500 mg thrice in a day) and Haritaki Churana (3 gm twice daily in cases of dyslipidemia) with lukewarm water for 12 weeks. So, the daily intake of the medicine was similar in all these cases. Hematological parameters, viz., lipid profile, and safety parameters were assessed at baseline and at the end of 12 weeks. Paired sample t-test was applied to compare the changes. Results: At the end of 12 weeks, compared with baseline, no statistically significant difference was observed in liver function tests (LFTs) and kidney function tests (KFTs) in the subjects. Conclusion: The findings clearly indicate that Vyoshadi Guggulu and Haritaki Churna are clinically safe and tolerable in subjects with obesity and dyslipidemia belonging to different age groups, gender, geographical area, and different Prakrti.