Several plant extracts rich in pharmacologically active compounds have shown to antagonize venom of several species. Mangifera indica has been used against snakebite by the traditional healers. However, there is paucity of scientific data in support. In this study, we evaluated the antivenom potential of aqueous extract of stem bark of M. indica against D. russellii venom-induced pharmacological effects such as life myotoxicity, edema, LD50 etc. The extract inhibited the phospholipase, protease, hyaluronidase, 5'nucleotidase, ATPase and alkaline phosphomonoesterase activities with varying IC50 values. It significantly inhibited both metalloproteases and serine proteases activities. Further, the extract significantly reduced the myotoxicity of the venom, as evident by the reduction of serum creatin kinase and lactate dehydrogenase activities. Though the extract completely inhibited in vitro PLA2 activity, it was unable to completely inhibit in situ hemolytic and in vivo edema-inducing activities, usually brought about by PLA2s. In lethality studies, co-injection of the venom preincubated with the extract showed higher protection than the independent injection of venom, followed by the extract in the mice. However, in both the cases the extract -a cocktail of inhibitors significantly increased the survival time, when compared to that of mice injected (i.p) with the venom alone. These results encourage further studies on the potential use of cocktail of inhibitors in improving the treatment of snake envenomation. Further, this study substantiates the use of M. indica as an antidote against snakebite by the traditional healers.