Atopic dermatitis (AD), a chronic inflammatory skin disorder, remains a major therapeutic challenge in clinical practice. Its pathogenesis is primarily driven by dysregulated T helper 2 (Th2) immune responses and pathological accumulation of reactive oxygen species (ROS). Here, we demonstrated that Portulaca oleracea L.-derived exosome-like nanoparticles (PELNs) exerted potent anti-inflammatory effects on skin-associated cells. However, PELNs have limited antioxidant activity and poor skin barrier penetration. To address these limitations, we developed a dissolvable microneedle (MN) patch incorporating 4-amino-2,2,6,6-tetramethylpiperidinyloxy (4-amino-TEMPO) conjugated with hyaluronic acid (HA-TEMPO) as both an ROS-scavenging agent and a needle-forming matrix, combined with PELN for synergistic therapy. In vivo studies showed that this MN system (designated HA-TEMPO@PELN-MN) effectively attenuated cutaneous oxidative stress and suppressed pathological skin crusting. Notably, the HA-TEMPO@PELN-MN restored Th1/Th2 immune balance. Overall, the MN patch combines excellent biocompatibility, rapid drug release, and efficient delivery, offering a safe and controlled strategy for AD treatment.