Background: The COVID-19 pandemic has overburdened current healthcare system and highlighted the need to explore potent remedies in Traditional medicine systems. Kabasura Kudineer (KSK), a poly herbal Siddha medicine, has shown great potential in treating COVID-19.Objective: The objective of the study is to explore the safety and efficacy of Kabasura Kudineer in a preclinical model for COVID-19: Syrian Golden Hamsters.Methods: This research study investigates the in vivo efficacy and safety of the well-known antiviral Siddha medicine KSK as a powdered tablet on COVID-19 infected Syrian golden hamsters. A total of 19 female hamsters were infected with the virus cell culture through intranasal route. 4 out of 19 animals were mock controls, 5 were infection controls, 4 were treated with remdesivir and acted as positive controls and remaining 6 were treated with KSK. The hamsters were observed for any adverse events, followed by their sacrifice on day 4 after inoculation with the virus. The lung pathology and viral load was studied for each hamster.Results: Therapeutic use of intraperitoneal instillation of Siddha formulation KSK reduces SARS-CoV-2 viral load and associated gross clinical parameters. Results showed significant reduction of 65% in the viral load for the KSK arm as compared to the infection control.Conclusion: We observed that the animals treated with KSK exhibited less severe pathology compared to the untreated infected group. No toxicity or adverse events were observed in the KSK group. This pre-clinical study supports the safety and efficacy of KSK.Study Registration: FNDR’s Institutional Animal Ethics Committee (IAEC), Registration Number 2082/PO/Rc/S/19/CPCSEA