Nanotechnology is a rapidly developing field of research that studies materials having dimensions of less than 100 nanometers. It is applicable in many areas of life sciences and medicine including skin care and personal hygiene, as these materials are the essential components of various cosmetics and sunscreens. The aim of the present study was to synthesize Zinc oxide (ZnO) and Titanium dioxide (TiO2) nanoparticles (NPs) by usingCalotropis procera(C. procera) leaf extract. Green synthesized NPs were characterized by UV spectroscopy, Fourier transform infrared (FTIR), X-ray diffraction (XRD), and Scanning Electron Microscopy (SEM) to investigate their structure, size, and physical properties. The antibacterial and synergistic effects of ZnO and TiO2NPs along with antibiotics were also observed against bacterial isolates. The antioxidant activity of synthesized NPs was analyzed by their α-diphenyl-β-picrylhydrazyl (DPPH) radical scavenging activity. In vivo toxic effects of the synthesized NPs were evaluated in albino mice at different doses (100, 200, and 300 mg/kg body weight) of ZnO and TiO2NPs administered orally for 7, 14, and 21 days. The antibacterial results showed that the zone of inhibition (ZOI) was increased in a concentration-dependent manner. Among the bacterial strains,Staphylococcus aureusshowed the highest ZOI, i.e., 17 and 14 mm against ZnO and TiO2NPs, respectively, whileEscherichia colishowed the lowest ZOI, i.e., 12 and 10 mm, respectively. Therefore, ZnO NPs are potent antibacterial agents compared to TiO2NPs. Both NPs showed synergistic effects with antibiotics (ciprofloxacin and imipenem). Moreover, the DPPH activity showed that ZnO and TiO2NPs have significantly (p> 0.05) higher antioxidant activity, i.e., 53% and 58.7%, respectively, which indicated that TiO2has good antioxidant potential compared to ZnO NPs. However, the histological changes after exposure to different doses of ZnO and TiO2NPs showed toxicity-related changes in the structure of the kidney compared to the control group. The current study provided valuable information about the antibacterial, antioxidant, and toxicity impacts of green synthesized ZnO and TiO2NPs, which can be influential in the further study of their eco-toxicological effects.