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The menace of the enfeebling disease leishmaniasis prevails due to the inaccessibility of effective vaccine and chemotherapy. Hence in the pursuit of finding novel alternative options with reasonable efficacy, immunomodulation, leishmanicidal activity and fewer side effects, screening of compounds from natural sources is needed. This study was focused on in vitro and in vivo antileishmanial screening of gallic acid (GA) against Leishmania donovani infection in BALB/c mice. GA showed in vitro parasiticidal activity and IC50 value of 19.59 ± 0.74 µg/ml and is able to arrest cell cycle at the sub‐G0/G1 phase. The therapeutic potential of gallic acid was assessed in the L. donovani‐infected BALB/c mice. GA reported a reduction in parasite burden and augmentation of CD4+ and CD8+ T lymphocytes. Also, the polarization of mouse immune status to protective Th1 response was evidenced by increased delayed‐type hypersensitivity response and levels of IgG2a, reactive oxygen species and nitric oxide. GA was reported to be safe and non‐toxic to human cell line THP‐1 and also to the liver and kidney of mice. Hence, the findings of the present study indicate the possible role of GA in the strengthening of host immune system and thus facilitating the clearance of leishmanial infection and conferring protection.