This article reviews the current trends and future perspectives of functionalized ZnO-based nanocomposites in biomedical applications. ZnO nanoparticles possess unique physicochemical properties, including high chemical stability, wide bandgap, and excellent biocompatibility, making them suitable for a variety of biomedical uses. The article discusses various synthetic approaches for producing ZnO nanoparticles, including mechanochemical, laser ablation, hydrothermal, sol-gel, emulsion/microemulsion, controlled precipitation, and green/biosynthesis methods. Each method is evaluated for its effectiveness in producing ZnO nanoparticles with desired properties. The article also explores the modification of ZnO nanoparticles to enhance their functionality for biomedical applications, such as biosensing, bioimaging, drug delivery, and tissue engineering. The modification approaches include surface modification with polymers, carbon quantum dots, and other metal nanoparticles, as well as the incorporation of functional groups to improve the nanoparticles' properties. The article also addresses the toxicity mechanisms of ZnO nanoparticles, emphasizing their neurotoxic potential and the pathways of toxicity. Overall, the review highlights the potential of ZnO-based nanocomposites in biomedical applications and the need for further research to fully understand their properties and applications.This article reviews the current trends and future perspectives of functionalized ZnO-based nanocomposites in biomedical applications. ZnO nanoparticles possess unique physicochemical properties, including high chemical stability, wide bandgap, and excellent biocompatibility, making them suitable for a variety of biomedical uses. The article discusses various synthetic approaches for producing ZnO nanoparticles, including mechanochemical, laser ablation, hydrothermal, sol-gel, emulsion/microemulsion, controlled precipitation, and green/biosynthesis methods. Each method is evaluated for its effectiveness in producing ZnO nanoparticles with desired properties. The article also explores the modification of ZnO nanoparticles to enhance their functionality for biomedical applications, such as biosensing, bioimaging, drug delivery, and tissue engineering. The modification approaches include surface modification with polymers, carbon quantum dots, and other metal nanoparticles, as well as the incorporation of functional groups to improve the nanoparticles' properties. The article also addresses the toxicity mechanisms of ZnO nanoparticles, emphasizing their neurotoxic potential and the pathways of toxicity. Overall, the review highlights the potential of ZnO-based nanocomposites in biomedical applications and the need for further research to fully understand their properties and applications.