The objective of this study is to develop beeswax-based solid lipid nanoparticles (SLNs) containing meglumine antimoniate (MA), curcumin (CUR), and 4-nitrochalcone (4NC) and evaluate their physicochemical characteristics, encapsulation efficiency, morphology, thermal properties, and in vitro leishmanicidal activity against promastigote forms of L. infantum and L. amazonensis. The average size of the SLNs prepared using the water/oil/water (W/O/W) double emulsion method ranged from 211 to 283 nm with semi-spherical geometry observed by TEM and colloidal stability measured by zeta potential. The formulations presented a high encapsulation efficiency for CUR and 4NC (up to 99%), while for MA, this efficiency was close to 20%. No physicochemical interaction between the drugs and lipids was observed by FTIR spectroscopy. DSC and TGA thermal analysis indicated that the thermal properties of the SLNs were different than those of pure beeswax, suggesting molecular reorganization during SLN formation. The cytotoxicity of the free and encapsulated drugs was evaluated on J774.1 macrophage cells, and no significant toxicity was observed at 1, 5, and 10 µM. Only the free CUR and 4NC caused a significant reduction in viability against promastigote forms of L. infantum and L. amazonensis, while the SLNs did not exhibit observable effects. In conclusion, the study indicated that the SLNs produced by the W/O/W double emulsion approach have promising characteristics for biomedical applications. Despite these positive attributes, additional research is required to establish these formulations as viable candidates for antileishmanial therapy.