Context <p>The protozoan parasite <i>Leishmania donovani</i> is a major causative agent of visceral leishmaniasis (VL), a lethal disease posing significant public health challenges globally. Existing anti-VL drugs have become increasingly ineffective due to rising drug resistance, underscoring the urgent need for novel and effective therapeutic candidates. Computational approaches offer rapid and systematic methods for identifying potential drug targets and supporting rational drug design. This review discusses in silico molecular docking studies targeting various <i>Leishmania</i> proteins and their inhibitors, alongside the in vitro and in vivo validation of selected compounds, emphasizing their crucial roles in advancing antileishmanial drug discovery.</p> Methods <p>In the review, we have focused on a molecular docking study and explored potential compounds with high binding energy toward protein targets of <i>Leishmania</i>. Following the in silico screening, our review highlights compounds that exhibit both in vitro and in vivo antileishmanial properties, allowing for an assessment of their therapeutic efficacy. Different Software is available for molecular docking, has been mentioned in the review. Overall conclusion of this review supports the computational approach in drug discovery before the in vitro and in vivo study, which can save cost and time efficiency as well.</p> Graphical Abstract <p></p>