Androgenetic alopecia (AGA) is the most common type of hair loss, and there is a lack of ideal treatment options. The damage and shedding of hair follicles are closely associated with niche dysregulation, including reactive oxygen species (ROS) accumulation, microvascular damage, and persistent inflammation. In this study, a biocomposite microneedle system comprising hypoxic extracellular vesicle (EV)-encapsulated selenium nanozyme (Se-HEVs-AMN) was designed to create a favorable perifollicular microenvironment. The novel Se-HEVs-AMN biocomposite patch features microneedles with sufficient mechanical strength, tailored dissolution properties, and a convenient detachable backing layer. The microneedles are modified with Astragalus polysaccharide (APS) and loaded with hypoxia-induced EVs containing selenium nanozyme. When applied to the dorsal skin of AGA mice, the microneedles rapidly dissolve, releasing active ingredients that increase hair density and enlarge hair follicle diameter through regulating inflammation, promoting angiogenesis, scavenging ROS, and resisting androgen.