In this study, we report that the FDA-approved non-peptide opioid antagonist drug (Vickers & Jolly, 2006), naltrexone in low dose (LDN) suppresses high fat/LPS induced pro-inflammatory cytokine release both from macrophage cells and Adipose tissue macrophages (ATMs). The naltrexone is already an FDA approved drug and thus the pharmacology (pharmacokinetics and pharmacodynamics) of naltrexone is well known and reported elsewhere (Gonzalez & Brogden, 1988; Toljan and Vrooman, 2018). LDN also showed activity as an ERK1/2 inhibitor. Moreover, virtual docking and simulation data also suggest LDN may disrupt the interaction of ACE2 with RBD. As a reliable COVID-19 vaccine is unlikely to available before the maximal infection of COVID-19 has occurred, it is essential to establish therapeutics for the COVID-19 patients, based on our data, we proposed FDA-approved LDN can be used in combination or as an adjuvants therapy to treat mild to moderate symptomatic COVID-19 patients