Background: Visceral leishmaniasis (VL), the deadliest form of leishmaniasis, remains endemic in tropical/subtropical regions. Conventional treatments are limited by toxicity, high cost, and emerging drug resistance. Methods: Studies published between 2000–2024 on antileishmanial efficacy of herbal extracts, synthetic drugs, and nanoformulations (liposomes, polymeric nanoparticles, metallic nanocarriers) were analyzed via databases including PubMed, Scopus, and Web of Science following PRISMA guidelines. Results: Gold-standard therapies like liposomal amphotericin‑B (AmBisome®) remain vital but require improved targeting and reduced toxicity. Phytocompounds from Azadirachta indica, Curcuma longa, and Withania somnifera exhibit significant in vitro/in vivo antileishmanial activity. Nanocarriers—liposomes, solid-lipid NPs, polymeric dendrimers, metallic nanoparticles—enhance bioavailability, reduce off‑target effects, and support targeted macrophage uptake. Patents focus on curcumin‑PLGA systems, dendrimer‑mediated combination therapies, and ligand-targeted delivery. Conclusion: Integrating low‑toxicity phytochemicals with nanotechnology platforms offers a promising, next-generation approach to treat VL. Future preclinical standardization and clinical trials are urgently needed. Graphical Abstract