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Objectives: The primary objective of this study is to compare the effects of 120-nanometer prenatal mesenchymal stem cell-derived exosomes with non-crosslinked hyaluronic acid on key dermatological parameters, including transepidermal water loss (TEWL), erythema reduction, melanin content reduction, and skin elasticity improvement. The secondary objective is to assess the overall patient satisfaction and safety profile of both treatments when applied alongside microneedling sessions spaced four weeks apart, with results monitored one month post-treatment. Introduction: Microneedling has gained popularity for enhancing skin absorption and boosting regenerative processes, often paired with topical treatments like hyaluronic acid (HA) to improve hydration and skin texture. However, prenatal MSC-derived exosomes may offer superior benefits due to their ability to deliver growth factors, cytokines, and miRNAs directly into the skin. This study seeks to investigate whether prenatal MSC-derived exosomes outperform non-crosslinked HA in reducing TEWL, erythema, and melanin levels, while also improving skin elasticity in patients treated with microneedling. Materials / method: This randomized, controlled study involved 44 patients with visible skin aging signs, divided into two groups (22 per group). Group A received 120-nanometer prenatal MSC-derived exosomes, while Group B received non-crosslinked hyaluronic acid. Both treatments were applied after microneedling (using <1.5mm needles) at four-week intervals for three sessions. TEWL, erythema, melanin, and skin elasticity were measured with a Tewameter, Mexameter, and Cutometer. Results were monitored one month post-treatment. Statistical analysis included paired t-tests, ANOVA, and p-value comparisons, with signif Results: In Group A (exosomes), TEWL decreased by 18.5%, erythema reduced by 25%, melanin levels dropped by 20%, and skin elasticity improved by 22%. In contrast, Group B (HA) showed a 10.3% decrease in TEWL, 15% reduction in erythema, 12% melanin reduction, and 13% improvement in elasticity. Statistically significant differences between the two groups were observed across all parameters (p<0.05), with prenatal MSC-derived exosomes demonstrating superior performance in reducing TEWL, erythema, melanin content, and improving skin elasticity compared to HA. Conclusion: This study concludes that prenatal MSC-derived exosomes significantly outperform non-crosslinked hyaluronic acid in reducing TEWL, erythema, and melanin levels, while enhancing skin elasticity when combined with microneedling. The exosomes' superior regenerative potential, likely due to their enriched content of bioactive molecules, makes them a more effective treatment for improving skin health. These findings suggest that exosome therapy may offer a more comprehensive skin rejuvenation strategy than HA, particularly for patients seeking advanced anti-aging interventions.