This review article discusses the development and applications of alginate-based electrospun nanofibers in drug delivery systems. Alginate, a natural polymer with excellent biocompatibility and biodegradability, has been explored for various biomedical applications due to its sustainable and promising properties compared to petroleum-derived polymers. However, the non-spinnability of pure alginate solutions has limited its practical use. To address this, synthetic polymers like poly(ethylene oxide) (PEO) and polyvinyl alcohol (PVA) are used as co-spinning agents to enhance the spinnability of alginate. Electrospinning technology, particularly multi-fluid electrospinning, has enabled the creation of diverse fiber structures, such as coaxial, Janus, and tertiary structures, which improve the spinnability of natural polymers and facilitate controlled drug release. The article highlights the advantages of electrospun alginate nanofibers (EANFs) in achieving various controlled release modes, including pulsed release, sustained release, biphasic release, responsive release, and targeted release. These release modes are crucial for optimizing therapeutic outcomes in different medical applications. For instance, pulsed release is effective for rapid drug delivery in acute injuries, while sustained release ensures a steady drug concentration over an extended period. Biphasic release combines rapid and sustained release to balance therapeutic efficacy and safety. Responsive release allows the drug release rate to change based on environmental conditions, and targeted release ensures drugs are delivered to specific sites. The review also discusses the challenges and advancements in the preparation of EANFs, including the modification of alginate to improve its spinnability and the design of complex fiber structures. The combination of electrospinning and other technologies, such as electrospraying, further enhances the drug loading and release capabilities of EANFs. The article concludes by emphasizing the potential of EANFs in various biomedical fields, such as tissue engineering, regenerative medicine, and drug delivery, and the ongoing research efforts to optimize their performance.This review article discusses the development and applications of alginate-based electrospun nanofibers in drug delivery systems. Alginate, a natural polymer with excellent biocompatibility and biodegradability, has been explored for various biomedical applications due to its sustainable and promising properties compared to petroleum-derived polymers. However, the non-spinnability of pure alginate solutions has limited its practical use. To address this, synthetic polymers like poly(ethylene oxide) (PEO) and polyvinyl alcohol (PVA) are used as co-spinning agents to enhance the spinnability of alginate. Electrospinning technology, particularly multi-fluid electrospinning, has enabled the creation of diverse fiber structures, such as coaxial, Janus, and tertiary structures, which improve the spinnability of natural polymers and facilitate controlled drug release. The article highlights the advantages of electrospun alginate nanofibers (EANFs) in achieving various controlled release modes, including pulsed release, sustained release, biphasic release, responsive release, and targeted release. These release modes are crucial for optimizing therapeutic outcomes in different medical applications. For instance, pulsed release is effective for rapid drug delivery in acute injuries, while sustained release ensures a steady drug concentration over an extended period. Biphasic release combines rapid and sustained release to balance therapeutic efficacy and safety. Responsive release allows the drug release rate to change based on environmental conditions, and targeted release ensures drugs are delivered to specific sites. The review also discusses the challenges and advancements in the preparation of EANFs, including the modification of alginate to improve its spinnability and the design of complex fiber structures. The combination of electrospinning and other technologies, such as electrospraying, further enhances the drug loading and release capabilities of EANFs. The article concludes by emphasizing the potential of EANFs in various biomedical fields, such as tissue engineering, regenerative medicine, and drug delivery, and the ongoing research efforts to optimize their performance.