Background and aims: The balm of Gilead, steeped in cultural significance, remains enigmatic due to its undefined composition and preparation methods. This study aims to recreate a formulation inspired by this elusive balm, combining historical insights with modern botanical knowledge. Methods: The study employed Populus balsamifera seeds infused with organic olive oil, mirroring historical practices. Essential oils—myrrh, frankincense, and cedar—were selected. Evaluation encompassed appearance, texture, aroma, and pH alignment with historical context and dermatological compatibility. Results: The formulated balm exhibited a smooth texture, earthy aroma, and a pH of 5.5, akin to skin’s natural acidity. These attributes echoed historical practices and holistic approaches. Conclusion: While the formulation mirrors historical attributes, challenges persist due to the genuine balm’s undefined composition. The study highlights the potential of employing Populus balsamifera due to limitations. Future directions include chemical analyses and clinical studies to validate therapeutic potential, bridging historical wisdom with contemporary science.