Leishmaniasis is one of the most neglected tropical diseases that present areal public health problems worldwide. Chemotherapy has several limitations such as toxic side effects, high costs, frequent relapses, the development of resistance and the requirement for long-term treatment. Effective vaccines or drugs to prevent or cure the disease are not available yet. Therefore, it is important to dissect antileishmanial molecules that present a selective efficacy and tolerable safety. The aim of this review is to update and summarize the investigations that have been undertaken on the antileishmanial activity of alkaloid compounds and their derivatives from January 1990 to September 2022. In this review, 183 alkaloid compounds have been identified with anti-Leishmania activities against amastigotes and/or promastigotes of different species. with respect to the test methods, 83.6% of studies were carried in vitro, while 16.4% of them were performed using in vivo assays. For in vitro assay, 153 alkaloid compounds were screened in vitro for anti-leishmanial activities against different Leishmania species (L. infantum, L. tropica, L. major, L. amazonensis, L. donovani, L. braziliensis, L. panamensis, L. guyanensis, L. chagasi and L. mexicana) and life cycle forms (amastigotes and/or promastigotes). The IC50 value for in vitro assay was in a range of 0.13 to 100 μg/ml, among 226 test studied, the highly active was found 62.3% (141), moderately and weak activity represent 31.5% (71) and 6.2 % (14) respectively. For in vivo assay, among 30 alkaloid compounds were studied in vivo against cutaneous and visceral leishmania of different species. The highest activity against cutaneous leishmaniasis was exhibited by Berberine (0.5% cream, twice a day for 35 days, Topically) against L. major which produced 99.9% reduction of parasites load in the skin and the highest activity against visceral leishmaniasis was shown by the 2-n-propylquinoline (oral administration at 0.54 mmol/kg for 5 and 10 days) against L. donvani which suppresses liver parasites by 87.8 and 99.9%, respectively. In conclusion, numerous alkaloid compounds have demonstrated a diverse range of activities against leishmaniasis with strong activities (IC50 <10 μg/mL). These compounds provide promising potential sources and reasonable starting points for the development of effective and affordable novel drugs.