Recently emerged coronavirus, known as SARS-CoV-2 or Covid-19 is considered as a serious threat for human health. Due to unavailable specific drugs for this virus, there is an urgent need for supportive cares. Epigenetic immune boosting approaches and developing anti-inflammatory agents by gut-associated bioactive macronutrients can be plausible protective cares for COVID-19. Suitable intake of bioactive macronutrients including prebiotics, fatty acids, proteins and branched-chain amino acids may result in anti-viral responses through modulating macrophages and dendritic cells via Toll-like receptors, decreasing viral load, inactivating the enveloped viruses, increasing the anti-inflammatory metabolites and inhibiting the proliferation of microbial organisms. Bioactive macronutrients may help in promotion of immunological responses and recovery acceleration against Covid-19. This review focuses on the mechanisms of bioactive macronutrients and related clinical trials on enveloped viruses with emphasis on gut-microbiome-immune axis. Macronutrients and this axis may be conducive strategies to protect host against the viral infection.