This study investigated the biological activities of Plumeria acuminata absolute (PLA), Pandan amaryllifolius absolute (PDA), and the essential oil blends (EOB2, EOB5) combining PLA, PDA, and other essential oils. It also aimed to identify the selected EOB for GC-MS analysis, develop this EOB into a cream, and determine its stability. Additionally, clinical evaluations were conducted to evaluate the cream’s efficacy on skin moisture, wrinkles, and irritation. PLA, PDA, and EOB2 exhibited potent anti-oxidants and anti-aging effects. They effectively showed free radicals scavenging (DPPH, ABTS), inhibiting lipid peroxidation, and suppressing hyaluronidase and collagenase activities. Due to its superior stability, EOB2 was selected for subsequent analysis. It demonstrated a potent inhibitory activity against MMP-2 enzymes. From GC-MS analysis, limonene was identified as the main component in EOB2. The 1.5%EOB cream maintained excellent stability under accelerated conditions. From the clinical study tested in 20 healthy volunteers after 8 weeks of twice diary application, it was found that the cream containing 1.5%EOB2 did not cause any skin irritation and significantly improved skin hydration. It also showed statistically significant decreases in wrinkle area, wrinkle depth, and skin roughness compared to the baseline. In conclusion, cream containing EOB could be a promising cosmeceutical or spa product for anti-aging purposes.