Urtica dioicais a perennial herb from the family of Urticaceae that is commonly known as stinging nettle. This plant is widespread in Europe, Africa, America, and a part of Asia, as it adapts to different environments and climatic conditions. The leaves, stalk, and bark ofU. dioicafound applications in the field of nutrition, cosmetics, textile, pest control and pharmacology. In this connection, bioactive chemical constituents such as flavonoids, phenolic acids, amino acids, carotenoids, and fatty acids have been isolated from the plant. With this review, we aim at providing an updated and comprehensive overview of the contributions in literature reporting computational, in vitro, pre-clinical and clinical data supporting the therapeutic applications ofU. dioica. Experimental evidence shows thatU. dioicaconstituents and extracts can provide neuroprotective effects by acting through a combination of different molecular mechanisms, that are discussed in the review. These findings could lay the basis for the identification and design of more effective tools against neurodegenerative diseases.Graphical Abstract