<p>Growing environmental concerns and the limitations of conventional chemical synthesis have accelerated interest in green nanotechnology, particularly the plant-mediated production of zinc oxide nanoparticles (ZnO NPs). This review aims to examine the sustainability and scientific advantages of green synthesis and consolidate current findings on the mechanisms, characteristics, and biomedical applications of plant-derived ZnO NPs. The most significant results highlight that phytochemicals in plant extracts act as natural reducing and stabilising agents, enabling controlled nanoparticle formation with enhanced biocompatibility, improved stability, and superior ROS-mediated antimicrobial and anticancer activities compared to chemically synthesised ZnO. Characterisation studies have consistently demonstrated the influence of particle size, crystallinity, and surface chemistry on therapeutic efficacy. Furthermore, recent research has reported the promising potential of green ZnO NPs in targeted drug delivery, antimicrobial coatings, antioxidant therapy, photocatalytic degradation, antimalarial parasites, urinary tract infection (UTI), toxicology, and cancer treatment. Despite these advantages, challenges remain in achieving scalable production, reproducibility and comprehensive toxicity evaluation. Overall, this review concludes that plant-mediated ZnO NPs represent a sustainable and effective nanomaterial platform with strong biomedical and environmental relevance, while emphasizing the need for standardized synthesis protocols and future in vivo studies.</p>