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Shuqi Gao,1,2,* Zhe Sui,3,* Qian Jiang,1,2 Yueyao Jiang1 1Department of Pharmacy, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China; 2School of Pharmacy, Jilin University, Changchun, Jilin Province, 130021, People’s Republic of China; 3Department of Radiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yueyao Jiang, Department of Pharmacy, China–Japan Union Hospital of Jilin University, Changchun, Jilin Province, 130033, People’s Republic of China, Tel +86 13844817007, Email jyy0705@jlu.edu.cnAbstract: Niosomes are key nanocarriers composed of bilayer vesicles formed by non-ionic surfactants and cholesterol, offering advantages such as high physicochemical stability, biodegradability, cost-effectiveness, and low toxicity. This review discusses their significant role in drug delivery, including applications in anticancer therapy and vaccine delivery. It also highlights the impact of non-ionic surfactants on niosome formation, drug delivery pathways, and protein corona formation—a relatively underexplored topic. Furthermore, the application of artificial intelligence in optimizing niosome design and functionality is examined. Future research directions include enhancing formulation techniques, expanding application scopes, and integrating advanced technologies. This review provides comprehensive insights and practical guidance for advancing niosome-based drug delivery systems. Keywords: niosomes, non-ionic surfactant, drug delivery systems, niosome functionalization