The escalating global burden of tuberculosis necessitates radical strategies to curb its spread. In this study, rifampicin (RIF), a first line anti-tubercular antibiotic and curcumin (CUR), a promising antimycobacterial compound were co-encapsulated in polymeric nanoparticles to achieve intramacrophage delivery and improved Mycobacterium tuberculosis clearance. The dual loaded nanoparticles revealed average size ~400 nm, low polydispersity and zeta potential of –26.89 ± 2.9 mV. Near complete release of both drugs from nanoparticles in artificial lysosomal fluid proposed drug release after macrophage internalisation. Nanoparticles were nontoxic to RAW 264.7 macrophages and aided 1.5-fold higher drug internalisation compared to free drugs. Enriched intracellular internalisation and lysosomal presence of nanoparticles was ascertained by confocal microscopy. Comparable minimum inhibitory concentration (MIC) of free RIF and CUR and nanoparticle encapsulated RIF and CUR confirmed retention of drug properties. High efficacy against Mycobacterium tuberculosis infected macrophages with RIF-CUR nanoparticles at 25x MIC (98.03 ± 2.5%), with complete clearance above 50x MIC suggests the dual loaded nanoparticles as a promising new nanosystem for tackling tuberculosis.