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Climatic changes and heat stress have become a great challenge in the livestock industry, negatively affecting, in particular, poultry feed intake and intestinal barrier malfunction. Recently, phytogenic feed additives were applied to reduce heat stress effects on animal farming. Here, we investigated the effects of ginseng extract using various in vitro and in vivo experiments. Quantitative real-time PCR, transepithelial electrical resistance measurements and survival assays under heat stress conditions were carried out in various model systems, including Caco-2 cells, <i>Caenorhabditis elegans</i> and <i>jejunum</i> samples of broilers. Under heat stress conditions, ginseng treatment lowered the expression of <i>HSPA1A</i> (Caco-2) and the heat shock protein genes <i>hsp-1</i> and <i>hsp-16.2</i> (both in <i>C. elegans</i>), while all three of the tested genes encoding tight junction proteins, <i>CLDN3</i>, <i>OCLN</i> and <i>CLDN1</i> (Caco-2), were upregulated. In addition, we observed prolonged survival under heat stress in <i>Caenorhabditis elegans</i>, and a better performance of growing ginseng-fed broilers by the increased gene expression of selected heat shock and tight junction proteins. The presence of ginseng extract resulted in a reduced decrease in transepithelial resistance under heat shock conditions. Finally, LC-MS analysis was performed to quantitate the most prominent ginsenosides in the extract used for this study, being Re, Rg1, Rc, Rb2 and Rd. In conclusion, ginseng extract was found to be a suitable feed additive in animal nutrition to reduce the negative physiological effects caused by heat stress.