As media reports have noted, the COVID-19 pandemic has accelerated market mainstreaming of immune-boosting food bioactives, supplements, and nutraceuticals. However, most studies reporting on the potential of bioactives against COVID-19 transmission have been uploaded as preprints with little opportunity to revise content for benefit and impact. The current review discusses current best evidence and information underpinning the role of food ingredients and bioactive compounds in supporting immune functions in humans and animals, specifically in the prevention and treatment of COVID-19 disease. Up to now, some evidence from randomized population and clinical trials has suggested that vitamin D levels may be linked to COVID-19 transmission and severity. Numerous theoretical studies have pointed to polyphenols and particularly flavonoids as potential inhibitors of SARS-CoV-2 infection. There is also inconclusive evidence to support the future use of β-glucan to address COVID-19 due in part to variability in immune response arising from heterogeneity in polysaccharide branch and chain length for different sources and the absence of a standardized extraction method. To confirm the promising outcomes and hypotheses for bioactive compounds, more randomized and controlled clinical studies are needed. The results of such studies would have a profound effect on the prospects of food supplements and nutraceuticals as potential prophylaxis against COVID-19 and serve to help consumers to protect themselves during the post-lockdown recovery era.