Background: The first drug for the treatment of leishmaniasis is pentavalent antimony compounds which have great side effects. Objectives: This study aimed to assess apoptosis induction by HESA-A, an herbal marine compound in Leishmania major promastigotes. Methods: Leishmania major promastigotes were treated with HESA-A in different increasing concentrations ranged 1.625 - 120 µg/mL, and amphotericin B and the phenomenon of apoptosis in the parasite were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and DNA fragmentation tests. Results: The IC50 value of the compound and amphotericin B at 72 h were estimated at 2.81 µg/mL and 40 µg/mL, respectively. After 72 h of the adjacency of Leishmania major promastigotes with IC50 dose (2.81 µg/mL), the percentage of promastigotes in early and late apoptosis phases in the treated group was 5.4% and 60.4%, respectively. DNA fragmentation of Leishmania major promastigotes treated with 2.81 µg/mL for 72 h was observed. Conclusions: HESA-A, with significant induction of apoptosis in Leishmania major promastigotes, can be plausible in the treatment of cutaneous Leishmaniasis.