Corina Dalia Toderescu, Iulia Gabriela Cresneac, Alexandru Oancea, Svetlana Trifunschi, Melania Munteanu, Casiana Boru
Protein misfolding and aggregation represent key pathological mechanisms in neurodegenerative and systemic amyloid disorders, yet disease-modifying therapeutic strategies remain limited. In recent years, plant-derived nanomaterials have attracted increasing attention as multifunctional platforms capable of interacting with misfolded proteins and modulating aggregation-related pathways. This review examines the evolution of research between 2015 and 2025 on plant-derived nanomaterials—including green-synthesized metallic nanoparticles, plant extracellular vesicles, and phytochemical-based nano-delivery systems—in the context of protein misfolding disorders. The available literature was analyzed to identify principal mechanisms of action, experimental models, and emerging therapeutic perspectives. Current evidence suggests that these nanomaterials may influence protein aggregation through direct molecular interactions, modulation of oxidative stress and neuroinflammatory responses, and enhancement of cellular protein clearance processes. However, the field remains characterized by methodological heterogeneity, limited standardization, and insufficient translational validation. By synthesizing recent developments, this review highlights key research trends, mechanistic gaps, and future directions necessary for advancing plant-derived nanomaterials toward biomedical applications targeting protein misfolding diseases.