Green-synthesized nanoparticles can be applicable in designing an effective, efficient, and low-risk treatment for cancer. In this regard, we introduced a novel and eco-friendly method for preparing pure α-Bi2O3, Mn-doped Bi2O3, and Zn-doped Bi2O3 nanoparticles with potent cytotoxic activity through the application of Salvadora persica extract as the green reactive, reducing, and capping agent. The biosynthesis and characterization of our product was supported by the results of powder X-ray Powder Diffraction (PXRD), Energy Dispersive X-Ray (EDAX), Field Emission SEM (FESEM), Transmission Electron Microscopy (TEM), Fourier-Transform IR (FT-IR), and Raman anal. The outcomes of SEM anal. displayed the porous morphol. of pure α-Bi2O3 nanoparticles, whereas the doping of Zn and Mn turned their structure into a conical shape. The TEM results presented the hexagonal shape of pure α-Bi2O3 NPs with a particle size mean of 46 nm. Addnl., the Zn-doped Bi2O3 nanoparticles consisted spherical particles with 32 nm of size mean, while the Mn-doped Bi2O3 NPs were approx. hexagonal with a particle size mean of 41 nm. The success of doping process was proven by the EDX anal. Next to their high potential in cytotoxic performance against cancer cell line, the results of MTT assay confirmed the potent cytotoxic activity of synthesized nanoparticles against breast cancer (MCF-7) and human umbilical vein endothelial (HUVEC) cells as well. Considering these observations, these products can be suggested as a proper candidate for biol. and medical applications.