(1) Background: Routine use of antibiotics in livestock animals strongly contributed to the creation of multidrug-resistant Salmonella Typhimurium strains (STM). Vaccination is an alternative to the use of antibiotics but often suffers from low efficacy. (2) Methods: Here we investigated whether long-chain inulin (lcITF) and Lactobacillus acidophilus W37 (LaW37) can support vaccination efficacy against STM and if changes can be seen at the level of gut microbiota. Piglets received daily supplementation until sacrifice. Animals were vaccinated on day 25 after birth one day after weaning, and animals were challenged with STM on days 52-54. (3) Results: LcITF/LaW37 enhanced vaccination efficacy by 2-fold. Diarrhea was significantly lower in lcITF/LaW37 and lcITF groups. Feed efficiency post-weaning was higher for piglets that received lcITF. The LcITF/LaW37 group was characterized by higher relative abundance of members of the family Prevotellaceae and lower relative abundance of Lactobacillaceae in feces. Although strongest microbial effects were observed post STM challenge on day 55, the transient effects of the dietary interventions were also detected in early life, on day 10 after birth, and post-weaning on day 30. (4) Conclusions: These results show that vaccination in immune-immature animals can be enhanced with functional foods and can simultaneously promote piglet health in an ingredient-dependent fashion. Effects on microbiota of the interventions were observed during stress periods only and were associated mainly with diarrhea.