Nutraceuticals are products derived from food sources with health benefits in addition to their basic nutritional values. Many of them can positively affect and enhance the immune system, which is particularly pertinent in the current turbulent times of COVID-19. Not surprisingly, nutraceutical sales rose dramatically during the pandemic period. However, much research is still needed to understand how natural products interact with the immune system to clarify their chemical compositions, mechanisms of action, and effects on health and illnesses. This Special Issue provided an open forum for researchers to share their research findings in the growing interest in nutraceuticals. We received an overwhelming response with a total of 33 submissions, of which only nine original research papers and ten reviews were accepted after rigorous peer-review. The included articles research into natural substances of interest in nutraceuticals ranging from herbal medicine to vitamins to microbiota-derived metabolites. The investigated immune-related responses include cancer, neurological diseases, gastroenterological disorders, inflammatory conditions, and infections.