Technical Abstract: Traditionally, the application of prophylactic antibiotics has been successful in reducing infection-related morbidity and mortality in animal production. However, with increasing concerns over the widespread use of feed-added chemicals in animal production and the emergence of antibiotic resistant microbial pathogens in the fields, there is much interest to develop alternative methods of disease control in poultry production. In this regard, rapid progress has been achieved on the identification and commercial application of novel plant phytonutrients to boost innate immunity against infectious diseases and tumors in clinical medicine. In this study, we evaluated several phytonutrients isolated from various plant sources for their immunostimulatory activities using in vitro cultures of splenocytes, macrophages and tumors. Extracts from 4 different medicinal plants (Cinnamaldehyde, Capsicum, Shiitake, and Curcuma) were tested for their effects on various in vitro parameters of innate immunity such as lymphocyte proliferation, macrophage activation, cytokine secretion and the inhibition of tumor cell growth. All plant extracts tested stimulated lymphocyte proliferation and inhibited tumor cell growth compared to the medium control. Co-culture of macrophages with Cinnamaldehyde, Capsicum, and Shiitake induced nitric oxide production with Shiitake significantly inducing the expression of IL-1' and IL-6 transcripts. Stimulation of macrophages with Cinnamaldehyde and Curcuma significantly induced IL-15 and IL-12 transcripts, respectively. This report documents the immunological basis of health-promoting effects of these plants in poultry for the first time. Further studies on the nature of the immunomodulating activities of these phytonutrients will facilitate the development of novel dietary strategies to reduce economic losses due to infectious diseases in poultry.