SARS-CoV-2 infection has now become the world's most significant health hazard, with the World Health Organization declaring a pandemic on March 11, 2020. COVID-19 enters the lungs through angiotensin-converting enzyme 2 (ACE2) receptors, alters various signaling pathways, and causes immune cells to overproduce cytokines, resulting in mucosal inflammation, lung damage, and multiple organ failure in COVID-19 patients. Although several antiviral medications have been effective in managing the virus, they have not been effective in lowering the inflammation and symptoms of the illness. Several studies have found that epigallocatechin-3-gallate and melatonin upregulate sirtuins proteins, which leads to downregulation of pro-inflammatory gene transcription and NF-κB, protecting organisms from oxidative stress in autoimmune, respiratory, and cardiovascular illnesses. As a result, the purpose of this research is to understand more about the molecular pathways through which these phytochemicals affect COVID-19 patients' impaired immune systems, perhaps reducing hyperinflammation and symptom severity. PRACTICAL APPLICATIONS: Polyphenols are natural secondary metabolites that are found to be present in plants. EGCG a polyphenol belonging to the flavonoid family in tea has potent anti-inflammatory and antioxidative properties that helps to counter the inflammation and oxidative stress associated with many neurodegenerative diseases. Melatonin, another strong antioxidant in plants, has been shown to possess antiviral function and alleviate oxidative stress in many inflammatory diseases. In this review, we propose an alternative therapy for COVID-19 patients by supplementing their diet with these nutraceuticals that perhaps by modulating sirtuin signaling pathways counteract cytokine storm and oxidative stress, the root causes of severe inflammation and symptoms in these patients.