Purpose: To synthesize silver nanoparticles using rhizome extract (RE) of E. wallichii as a bioreductant and surfactant.Method: RE was used as a bio-reductant for the reduction of Ag+1 (aq.) and as a stabilizing agent for silver nanoparticles (AgNPs). The AgNPs were then characterized by UV-visible spectrophotometer, scanning electron microscopy (SEM), dynamic light scattering spectroscopy (DLS), x-ray diffraction (XRD), energy dispersive x-ray spectroscopy (EDS) and infrared (IR) spectroscopy. The antinociceptive potential of AgNPs was evaluated using Eddy’s hot plate. Spasmolytic bioassay was measured in mice via GI charcoal movement test. Anti-leishmanial potency was examined against promastigotes of Leishmania tropica, while antioxidant bioassay was determined using DPPH reduction method.Results: UV-Vis results showed characteristic surface plasmon resonance band from 440 – 460 nm, thus confirming the reducing ability of RE. SEM analysis showed spherical AgNPs with a typical face center cubic (fcc) structure as evidence by their x-ray diffraction (XRD) pattern. The role of RE as a stabilizing agent towards AgNPs was supported by IR and electronic absorption spectral data. Phytochemical investigation of RE confirmed the presence of alkaloids, flavonoids, phenols and glycosides etc. Mice treated with RE-AgNPs exhibited dose-dependent analgesic and spasmolytic effects. RE functionalized AgNPs exhibited promising antileishmanial and antioxidant effects (p < 0.05).Conclusions: RE-AgNPs exhibit substantial spasmolytic and antinociceptive activity, indicating central and peripheral analgesic effects. Thus, the formulation’s antileishmanial and antioxidative effects, indicate that it might be useful for preventing infectious and oxidative stress disorders.Keywords: Euphorbia wallichii, Silver nanoparticles, Antioxidant, Analgesic, Antispasmodic, Antileishmanial