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Background: The available drugs for treating visceral leishmaniasis are limited. Moreover, the disease is associated with suppression of immune function. Therefore, therapies with effective immunomodulatory agents are needed which can decrease parasitic burden and enhance adaptive immunity. Objectives: The present study was planned to evaluate the antileishmanial efficacy of crude ethanolic extract of roots of Chlorophytum borivilianum (CBREE) against murine visceral leishmaniasis through immunomodulation. Materials and methods: The in vitro studies were carried out to check leishmanicidal activity against promastigote form and cytotoxicity against HeLa cells. The parasite load in liver smears, immunological and biochemical changes induced by 500 and 1000 mg/kg b.wt. of CBREE were assessed on 1, 7, 14 and 21 post treatment days in infected and treated BALB/c mice. Results: CBREE showed inhibitory effect on growth of promastigotes with IC50 of 28.25 μg/mL and negligible cytotoxicity. The extract was toxicologically safe in BALB/c mice when administered orally with 5 g/kg b.wt. of extract. A significant reduction in parasite load was observed along with active immunomodulation through enhanced Th1 type of immune responses and suppressed Th2 type of immune responses. Conclusion: The treatment with both doses showed no toxic effect as evidenced by normal liver and kidney function tests and normal histological observations of liver and kidney. Therefore, it should be further explored for its active components in pursuit of the new effective antileishmanial agents in the plant kingdom. Keywords: Phytochemical constituents, Parasite load, Cytokine responses, Antibody responses, DTH responses, Histopathology