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Abstract Bioactive peptides are unique, low molecular weight peptide sequences generally consisting of 2–20 amino acid residues. These peptide sequences are inactive within the parent protein but they become physiologically active once released from the native polypeptide sequence via hydrolysis. There are multiple methods for producing bioactive peptides from precursor protein molecules, with microbial fermentation of various dietary matrices indubitably being a novel method to produce peptides with specialized bioactivity. Fermented foods especially fermented dairy products, legumes, cereals, meat and marine life as a source of bioactive peptides have been well documented. These peptides have gained scientific attention owing to their biofunctional attributes. The food-derived bioactive peptides have the potential to serve as valuable ingredients in functional foods and nutraceutical products to promote health. Bioactive peptides are known to possess various health-promoting properties including anti-carcinogenic, anti-hypertensive, anti-microbial, antioxidant, anti-diabetic, and immunomodulatory effects. The COVID-19 pandemic has put the world's health, economy, and social stability in jeopardy. The SARS-CoV-2 infection contributes to severe conditions and higher mortality in COVID-19 patients with comorbidities. The viral infection not only causes severe respiratory infection but also causes malfunctioning of the Renin-Angiotensin system (RAS), resulting in the downregulation of Angiotensin-converting enzyme II(ACE-II) and subsequent accumulation of Angiotensin II. Several synthetic ACE inhibitory medications are being used to minimize the severity of Angiotensin II adverse effects such as hypertension. The growing concern about the side effects associated with these pharmaceuticals has prompted researchers to look for alternatives in the form of foods and nutraceuticals with health-promoting features. Biologically active peptides have the potential to be used as a new-generation pharmaceutical product for various diseases including COVID-19. The multi-functional food-derived peptides could be a promising approach against COVID-19 infection in patients with chronic complications through their therapeutic actions. However, more in vitro and in vivo studies are required to validate their efficacy in enhancing the survivability and viability of COVID-19 patients. Although many peptides have demonstrated their positive effects via biochemical assays, cell culture, and animal models, the translation of these findings into practical application is limited. This might be related to the bioavailability issues, which influence the correlation of in vitro results with in vivo functions of peptides. To exert a health-promoting impact, these peptides need to withstand severe gastrointestinal conditions and the action of digestive enzymes to reach the target site in an active state. Therefore it is critical to thoroughly investigate the gastrointestinal stability and transport of these biopeptides and devise strategies to improve their absorption and bioavailability. Graphical Abstract |