Lactic acid bacteria are a group of taxonomically diverse, Gram-positive food-grade bacteria that have been safely consumed throughout history. The lactic acid bacterium Lactococcus lactis, well-known for its use in the manufacture of cheese, can be genetically engineered and orally formulated to deliver therapeutic proteins in the gastrointestinal tract. This review focuses on the genetic engineering of Lactococcus lactis to secrete high-quality, correctly processed bioactive molecules derived from a eukaryotic background. The therapeutic applications of these genetically modified strains are discussed, with special regards to immunomodulation.