The green synthesis of silver nanoparticles (AgNPs) using Elephantorrhiza elephantina (Burch) bulb extracts and evaluation of their antimicrobial, cytotoxic, and antioxidant properties were investigated. The crude plant extracts were prepared using distilled water, ethanol, and methanol for a comparison. Silver nanoparticles were synthesized and characterized via UV–Visible spectroscopy (UV–VIS), transmission electron microscopy (TEM), and X-ray diffraction (XRD). The formation of silver nanoparticles was confirmed using the UV–VIS spectra at 550 nm. The TEM confirmed the nanoparticle morphology as a mixed dispersed sphere, oval, and triangular shapes with a size range of 7.8 nm to 31.3 nm. The secondary metabolites were detected using TLC, DPPH, and LC-MS. Antimicrobial activity was assessed based on agar-well diffusion; cytotoxicity was examined through MTS assays. Various phytochemical constituents were detected through TLC and LC-MS. The crude extracts and methanol-extract-capped AgNP were able to scavenge free radicals, as shown by the developments of inhibitory bands on the TLC plate. The agar well diffusion test revealed that the AgNP capped methanol extract had potent antimicrobial activity against Gram-positive and Gram-negative multidrug resistant bacteria in comparison with penicillin and neomycin, with inhibition zones ranging between 10 mm and 14 mm for the methanol-extract-capped AgNP. The in vitro MTS assay revealed that methanol crude extracts and methanol-extract-capped AgNP had a less cytotoxic effect on the HEK293 cells in comparison with untreated cells (control). We therefore conclude that methanol was the best reducing solvent with the best overall nanoparticle morphology and performance in antimicrobial and cytotoxicity, in comparison to ethanol and distilled water.