Chagas disease and leishmaniasis are two neglected tropical diseases that affect millions of people in low- and middle-income tropical countries. These diseases caused by protozoan parasites pose significant global health challenges, which have been exacerbated by the recent COVID-19 pandemic. There is an urgent need for novel therapeutics as current treatments are limited by toxicity and drug resistance. Nucleoside analogues, which have been extensively studied and successfully applied in antiviral and antitumor therapies, hold potential that has yet to be fully explored for treating these neglected diseases. In this review, we discuss the use of nucleoside analogues as promising therapeutic agents for Chagas disease and leishmaniasis. After briefly examining the pathology, progression, and current treatment options for these diseases, we provide a comprehensive analysis of the status of nucleoside analogues and explore their prospects. By outlining the current landscape and future directions, this review aims to guide research and development efforts towards more effective nucleoside-based treatments for Chagas disease and leishmaniasis.