Lactic acid-producing bacteria are the most commonly used probiotics that play an important role in protecting the host against harmful microorganisms, strengthening the host immune system, improving feed digestibility, and reducing metabolic disorders. Lactobacillus fermentum (Lb. fermentum) is a Gram-positive bacterium belonging to Lactobacillus genus, and many reportedly to enhance the immunologic response as well as prevent community-acquired gastrointestinal and upper respiratory infections. Additionally, Lb. fermentum strains produce diverse and potent antimicrobial peptides, which can be applied as food preservative agents or as alternatives to antibiotics. Further functions attributed to probiotic Lb. fermentum strains are their abilities to decrease the level of blood stream cholesterol (as cholesterol-lowering agents) and to potentially help prevent alcoholic liver disease and colorectal cancer among humans. Finally, Lb. fermentum is a key microorganism in sourdough technology, contributing to flavor, texture, or health-promoting dough ingredients, and has recently been used to develop new foods stuffs such as fortified and functional foods with beneficial attributes for human health. Development of such new foodstuffs are currently taking important proportions of the food industry market. Furthermore, an increasing awareness of the consumers prompts the food-makers to implement alternative environmental friendly solutions in the production processes and/or suitable biological alternative to limit the use of antibiotics in feed and food. Here, we give an account on the application of Lb. fermentum strains in the biomedical and food preservation fields, with a focus on probiotic features such as bacteriocin production. We also summarize the use of Lb. fermentum as cell factories with the aim to improve the efficacy and health value of functional food.