Aim: This work aims to develop a mannosylated nanostructured lipid carrier (NLC) loaded with rifampicin to improve tuberculosis treatment. Materials & methods: An active targeting strategy was used and the nanoparticles were characterized. Effects on cell viability and the antimycobacterial activity of the nanoformulations were evaluated. Results: The nanoparticles developed exhibited a size of about 315 nm and polydispersity <0.2. The drug encapsulation efficiency was higher than 90% and its release was sensitive to pH. The mannosylated NLCs showed efficient uptake by bone marrow derived macrophages. Further, rifampicin-loaded mannosylated NLCs were more efficient in inducing a decrease of intracellular growth of mycobacteria. Conclusion: The NLCs developed can be used as a promising carrier for safer and efficient management of tuberculosis.