Background: Hyaluronic acid (HA) is a commonly used scaffolding material and has an important role in tissue regeneration. A biodegradable microneedle patch can deliver HA through the stratum corneum in a safe and easy manner. Objectives: To evaluate the safety and efficacy of biodegradable microstructure patches comprising cross-linked hyaluronic acid (CLHA). Methods: A total of 20 participants applied the CLHA patch on each crow’s foot and the nasolabial folds for 2-3 minutes. Water contents, anti-wrinkle effects, and cutaneous side effects were evaluated at 4 hours, 1 day, 3 days, and 6 days after patch application. Results: CLHA patches significantly improved skin hydration at the periorbital region for 3 days and at the nasolabial fold for 6 days after single application. Superficial wrinkles also exhibited improvement at the periorbital region for 3 days and at the nasolabial fold for 1 day after application. No side effects were reported in any of the study cases. Conclusion: CLHA microstructure patch can be used safely and conveniently for moisturization and anti-wrinkle effects.