Streptococcus thermophilus is widely used in dairy fermentation as a starter culture for yogurt and cheese production. Many strains are endowed with potential probiotic properties; however, since they might not survive in adequate amounts after transit through the human gastrointestinal tract, it is advisable to improve cell survivability during this passage. The present study evaluates the use of 2′-fucosyllactose, a prebiotic molecule from human milk, compared with other known molecules, such as gelatin and inulin, to form alginate-based microcapsules to fulfill these requirements. Such microcapsules, obtained by the extrusion technique, were evaluated in terms of encapsulation efficiency, storage stability, gastrointestinal condition resistance, and cell release kinetics. Results reveal that microcapsules made using 2′-fucosyllactose and those with inulin resulted in the most efficient structure to protect S. thermophilus strain TH982 under simulated gastrointestinal conditions (less than 0.45 log CFU/g decrease for both agents). In addition, a prompt and abundant release of encapsulated cells was detected after only 30 min from microcapsules made with sodium alginate plus 2′-fucosyllactose in simulated gastrointestinal fluid (more than 90% of the cells). These encouraging results represent the first report on the effects of 2′-fucosyllactose used as a co-encapsulating agent.