Probiotics have been increasingly recognized for positively influencing many aspects of human health. Lactiplantibacillus plantarum (L. plantarum), a non-pathogenic bacterium, previously known as Lactobacillus plantarum, is one of the lactic acid bacteria commonly used in fermentation. The probiotic properties of L. plantarum have highlighted its health benefits to humans when consumed in adequate amounts. L. plantarum strains primarily enter the body orally and alter intestinal microflora and modulate the immune responses in their host; thereby benefiting human health. Furthermore, the use of L. plantarum as vaccine vectors delivering mucosal antigens has been shown to be a promising strategy. These aspects, from Immunomodulation to vaccine delivery by L. plantarum in preclinical settings, are highlighted in this review. Along these lines, construction of a recombinant L. plantarum strain expressing a B cell multi-peptide, as a future vaccine to modulate immunity and confer anti-tumor effect by targeting Her-2/neu-overexpressing cancers in local and distal sites, is also presented and discussed.