Background: Skin aging is a complex process influenced by genetic, hormonal, and environmental factors. Exosome‐based therapies, particularly those derived from plant sources such as apples, have emerged as a promising alternative for promoting skin regeneration and improving skin health. Methods: A 12‐week prospective, non‐randomized, split‐face, self‐controlled trial was conducted with 21 participants aged 40–59 years. The right facial hemisphere received Exo‐V Professional combined with Microneedle Therapy System (MTS), while the left hemisphere was treated with microneedling and normal saline as a control. This side allocation was predefined and was not randomized. Participants underwent four treatment sessions at three‐week intervals. Skin improvement was assessed through objective measurements, including wrinkle depth, skin lifting, skin elasticity, hydration, skin brightness, pore size, texture, glossiness, and transepidermal water loss (TEWL). Histopathological evaluation was performed on ex vivo human skin samples to assess collagen synthesis. Subjective satisfaction was measured using a 5‐point Likert scale, and adverse reactions were monitored through clinical assessments. Results: The Exo‐V side exhibited significantly greater improvements in all measured parameters compared to the control side ( p < 0.05). Histological analysis confirmed enhanced collagen deposition in the Exo‐V side, with increased young collagen synthesis compared to the control. Subjective assessments showed 100% participant satisfaction, with no reported adverse skin reactions throughout the study. Conclusion: Exo‐V Professional applied after microneedling was associated with greater short‐term improvements in multiple facial skin parameters than microneedling with saline, suggesting its potential as a topical adjunctive approach for facial rejuvenation. Further randomized, blinded, vehicle‐controlled studies with longer follow‐up are needed to confirm these findings, clarify the underlying mechanisms, and assess the durability of the observed effects.