Tehran University of Medical Sciences Iranian Journal of Parasitology 1735-7020 17 4 2022 12 04 458 472 Abdullah Alanazi Department of Biological Sciences, Faculty of Science and Humanities, Shaqra University, Ad-Dawadimi, Saudi Arabia Mourad Ben Said 1. Department of Basic Sciences, Higher Institute of Biotechnology of Sidi Thabet, University of Manouba, Manouba 2010, Tunisia 2. Laboratory of Microbiology, National School of Veterinary Medicine, Sidi Thabet, University of Manouba, Manouba 2010, Tunisia 2022 04 29 2022 09 02 Background: This study was designed considering the challenges of leishmaniasis treatment and the benefits of carriers of drug delivery systems to review plant bioactive ingredients in delivery systems and nanocarriers for the treatment of leishmaniasis. Methods: The methodology of this review investigation followed the 06-PRISMA recommendations. The searches were carried out up to January 30, 2022, in the central English databases SCOPUS, WEB OF SCIENCE, EMBASE, PUBMED, and GOOGLE SCHOLAR using the search terms “ç”, “leishmaniasis”, “herbal medicines”, “drug delivery”, “nanocarriers”, “herbal compounds”, and “secondary metabolites”. Results: Out of 5731 articles, 19 publications, including 12 in vivo (63.15%), 3 in vitro (15.8%), and 4 in vitro/ in vivo (21.1%) up to 2022, fulfilled the criteria presence for argument in the current systematic study. Plant bioactive ingredients were curcumin, betulinic acid, artemisinin, 4-nitrobenzaldehyde thiosemicarbazone, andrographolide, pentalinonsterol, ursolic acid, amarogentin, carvacrol, 14-deoxy-11-oxo-andrographolide, quercetin, beta-lapachone, cedrol, 2ˊ,6ˊ-dihydroxy-4ˊ-methoxychalcone, and oleanolic acid. Conclusion: The high potential of plant bioactive ingredients in delivery systems due to the load on the nanocarrier for the treatment of leishmaniasis through some main mechanisms of action, e.g. changes in the fluidity and the structure of the cell wall, creation of reactive oxygen species (ROS) and mitochondrial dysfunction, inhibition of DNA topoisomerase I enzyme, minimal cytotoxicity, stimulation of cell cycle disruption, stimulation of apoptosis, enhancement of the immune system. However, further investigations, especially in the clinical setting, are required to confirm these findings. https://ijpa.tums.ac.ir/index.php/ijpa/article/view/3618 https://ijpa.tums.ac.ir/index.php/ijpa/article/download/3618/1245