Purpose <p>Gene editing technologies have emerged as a crucial approach totackling parasitic infections. Recent research underscores the potential of protozoan parasites, including <i>Leishmania</i>, to utilize gene editing strategies, such as the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins)(CRISPR/Cas9) to edit parasite genomes, modify virulence factors, and alter host immune responses. This review aims to explore the potential of CRISPR/Cas9 in the study of <i>Leishmania </i>and Leishmaniasis, focusing on its applications in understanding mechanisms and developing novel editing strategies.</p> Methods <p>The immunological response of the mammalian host and the nature of the <i>Leishmania </i>parasites play essential roles in the formation and progression of parasitic diseases. Among alternative treatment strategies, CRISPR/Cas9 has attracted attention as a promising tool for introducing protective or therapeutic mutations in Leishmaniasis. This review will provide recent insights into the role of gene editing, especially CRISPR/Cas9, in host-pathogen interactions, intercellular communication, immunomodulation, and pathogenesis of <i>Leishmania</i>.</p> Results <p>Current findings reveal that CRISPR/Cas9 enables efficient modification of <i>Leishmania </i>genomes, providing valuable insights into parasite biology, host-pathogen interactions, intercellular communication, immunomodulation, and disease pathogenesis. Additionally, immunotherapeutic models are being investigated to explore the potential applications of CRISPR/Cas9 in theranostics.</p> Conclusion <p>CRISPR/Cas9 has attracted attention as a promising tool for introducing protective or therapeutic mutations in Leishmaniasis. Integrating CRISPR/Cas9 with <i>Leishmania</i>-related research opens new avenues for disease control and understanding, while biologically inspired immunomodulatory strategies highlight its emerging role in next-generation parasite-targeted immunotherapy.</p>