Despite the widespread application of zinc oxide nanoparticles in biomedicine, their use is still a controversial issue. Zinc oxide nanoparticles were reported to have therapeutic benefits. However, they were reported to have toxicological hazards as well. Several studies reported the antibacterial, anticancer, antioxidant, and immunomodulatory effects of zinc oxide nanoparticles. Additionally, zinc oxide nanoparticles were used in sunscreens. Furthermore, the ability to use zinc oxide nanoparticles as an adjuvant treatment to alleviate the toxic effects of chemotherapeutic drugs has been reported. However, zinc oxide nanoparticles were shown to induce toxic effects in different body organs and systems. The affected organs included liver, spleen, kidney, stomach, pancreas, heart and lung. In addition, zinc oxide nanoparticles were reported to adversely affect the neurological system, lymphatic system, hematological indices, sex hormones levels, and fetal development. The toxic effects of zinc oxide nanoparticles were based on their concentration, their dose, the route of their administration, and the time of exposure to those particles. Thus, it is crucial to assess their efficacy and safety to determine their toxicological risks and therapeutic benefits.