Introduction:To date, no specific therapeutic drug has been approved to target SARS-CoV-2. Hence, it remains a major challenge to decide what potential therapeutic regimens to treat COVID-19 patients. This study aims to investigate curcumin and virgin coconut oil (VCO) effects on cytokine levels (IL-1β, IL-2, IL-6, IL-18, TNF-α, and IFN-β) in COVID-19 patients. Methods: This study was a single-center, controlled trial with a parallel Arm or a Randomized Clinical trial design. A total of sixty COVID-19 patients admitted to the Universitas Sebelas Maret Hospital, Surakarta, Indonesia, were divided into two groups. The first group, consisting of 30 patients, was treated with Azithromycin 500 mg + Oseltamivir 2×75 mg + Hydroxychloroquine 400 mg/day for 5 days. The second group, comprising 30 patients, was treated with Azithromycin 500 mg + Oseltamivir 2×75 mg + Hydroxychloroquine 400 mg/day for 5 days, added with VCO 30 mL and curcumin 3×1 g/day for 21 days. The cytokine profiles of the serum samples were analyzed by the enzyme-linked immunosorbent assay (ELISA) on days 1, 14, and 21. Results: Our study showed that the second group had a significant reduction in IL-1β, IL-2, IL-6, TNF-α, and IFN-β levels after being treated with standard therapy added with curcumin and VCO on day 21 (p<0.05). Conclusion: These results suggested that curcumin and VCO might benefit the treatment of COVID-19 patients.