Dongmin Yu, J. H. Park, Taeho Kim, Chanju Choi, Simseok A. Yuk, Hyungjun Kim
Phytochemicals have attracted considerable attention as therapeutically relevant bioactive compounds due to their diverse pharmacological activities, including anti-inflammatory, antioxidant, anticancer, and metabolic regulatory effects. However, their clinical translation is frequently hindered by unfavorable pharmaceutical properties such as poor aqueous solubility, chemical instability, rapid metabolism, and limited bioavailability. These challenges have constrained the reproducibility and therapeutic reliability of phytochemical-based interventions. In this context, nanotechnology-enabled delivery systems have emerged as effective strategies to overcome the intrinsic limitations of phytochemicals and enhance their biological performance. This review provides a comprehensive overview of recent advances in nanotechnology-based delivery platforms for phytochemicals, with emphasis on lipid-based nanocarriers, polymeric nanoparticles, nanoemulsions and self-nanoemulsifying drug delivery systems, inorganic and hybrid nanocarriers, as well as hydrogel-based and transdermal delivery systems. We discuss how rational nanocarrier design improves solubility, stability, pharmacokinetics, cellular uptake, and tissue targeting, thereby enhancing therapeutic efficacy across multiple disease areas. In addition, critical safety, toxicity, manufacturing, and regulatory considerations that influence translational potential are addressed. By adopting a delivery-centered perspective, this review highlights current challenges and future opportunities in nano-phytomedicine and underscores the importance of integrating nanotechnology, biological insight, and regulatory-conscious development to advance phytochemicals toward clinically viable therapeutic applications.