Abstract Growing concerns about antibiotic resistance coupled with recent legislation limiting in-feed antibiotic use in livestock feed has led to a resurgence of interest in plant-based extracts, prebiotics/probiotics, and other nutraceutical compounds with immune-modulating properties. Consumer preference for functional ingredients in their own food as well as feed for their pets or livestock has created a niche for development of feed additives with bioactive properties with the potential to improve health through their ability to regulate inflammation and modulate microbial communities. For example, dietary omega-3 fatty acids have been documented to reduce inflammation through altering the fatty acid composition of immune cells, shifting immune cell function, and reducing inflammatory lipid mediator and cytokine production. Dietary probiotic supplementation allows an intimate interaction between the gut mucosa and the largest concentrated population of the host’s immune cells, the mucosal immune system. Probiotics have been shown to modulate the inflammatory response through interaction with intestinal epithelial cells, M-cells in Peyer’s patches, innate immune cells such as dendritic and other antigen-presenting cells, and increasing barrier function through increased mucus and antibody production. Other feedstuffs such as green tea components (epigallocatechin-3-gallate, EGCG) interact with neutrophils and macrophages to limit cellular migration and inflammatory molecule production to reduce inflammation. A wealth of information detailing mechanistic outcomes exists in mouse literature and human cell lines, while livestock and companion animal literature is an untapped area for future work. An emphasis on research aimed at a more molecular, mechanistic understanding of currently available feed additives will lead to the improvement of existing additives and development of new additives for use in livestock and companion animal feed.