Vaccination is considered the most effective strategy for controlling tuberculosis (TB). The existing vaccine, the Bacille Calmette-Guérin (BCG), although partially protective, has a number of limitations. Therefore, there is a need for developing new TB vaccines and several strategies are currently exploited including the use of viral and bacterial delivery vectors. We have previously shown that
Lactobacillus plantarum
(
Lp
) producing Ag85B and ESAT-6 antigens fused to a dendritic cell-targeting peptide (referred to as
Lp
_DC) induced specific immune responses in mice. Here, we analyzed the ability of two
Lp
-based vaccines,
Lp
_DC and
Lp
_HBD (in which the DC-binding peptide was replaced by an HBD-domain directing the antigen to non-phagocytic cells) to activate antigen-presenting cells, induce specific immunity and protect mice from
Mycobacterium tuberculosis
infection. We tested two strategies: (i)
Lp
as BCG boosting vaccine (a heterologous regimen comprising parenteral BCG immunization followed by intranasal
Lp
boost), and (ii)
Lp
as primary vaccine (a homologous regimen including subcutaneous priming followed by intranasal boost). The results showed that both
Lp
constructs applied as a BCG boost induced specific cellular immunity, manifested in T cell proliferation, antigen-specific IFN-γ responses and multifunctional T cells phenotypes. More importantly, intranasal boost with
Lp
_DC or
Lp
_HBD enhanced protection offered by BCG, as shown by reduced
M. tuberculosis
counts in lungs. These findings suggest that
Lp
constructs could be developed as a potential mucosal vaccine platform against mycobacterial infections.