Neglected tropical diseases (NTDs) as termed by WHO include twenty different infectious diseases that are caused by bacteria, viruses, and parasites. Among these NTDs, Chagas disease and leishmaniasis are reported to cause high mortality in humans and are further associated with the limitations of existing drugs like severe toxicity and drug resistance. The above hitches have rendered researchers to focus on developing alternatives and novel therapeutics for the treatment of these diseases. In the past decade, several target-based drugs have emerged, which focus on specific biochemical pathways of the causative parasites. For leishmaniasis, the targets such as nucleoside analogs, inhibitors targeting nucleoside phosphate kinases of the parasite’s purine salvage pathway, 20S proteasome of Leishmania, mitochondria, and the associated proteins are reviewed along with the chemical structures of potential drug candidates. Similarly, in case of therapeutics for Chagas disease, several target-based drug candidates targeting sterol biosynthetic pathway (C14-ademethylase), L-cysteine protease, heme peroxidation, mitochondria, farnesyl pyrophosphate, etc., which are vital and unique to the causative parasite are discussed. Moreover, the use of nano-based formulations towards the therapeutics of the above diseases is also discussed. © Copyright © 2021 J, M and Chanda.