Background: Topical skin care products use various technologies to promote skin repair. Growth factors of human, animal, and plant-derived origins have clinically demonstrated the ability to repair skin by promoting collagen, elastin, and glycosaminoglycan (GAG) production to reconstruct and reinforce skin’s extracellular matrix (ECM). Human skin cells respond to instructions from highly specialized proteins or hormones referred to as growth factors. These growth factors initiate cellular communication that instigates cellular replication, production, or proliferation. The production of elastin and collagen dermal connective fibers slows, and, with age, the regenerative rates of GAGs become delayed. These biological issues can be exacerbated by extrinsic factors such as sun exposure, pollutants, and various other factors. Growth factor-based products have become important topical treatment modalities for addressing signs of skin aging such as fine lines, deep wrinkles, dryness, laxity, and textural irregularities. Objective: The aim of a 12-week clinical trial of a growth factor composition was to assess its effectiveness at restoring skin health through dermal and epidermal restructuring of aged skin. Results: Data from expert grading, and from corneometer and cutometer evaluations, as well as 2D and 3D image analysis, reflected significant improvements in facial skin appearance, firmness, elasticity, and hydration. Elements that improved most dramatically in investigators’ assessments included radiance, firmness, tactile elasticity, textural smoothness, overall appearance, and crow’s feet. Ultrasound imaging showed continual increases in dermal and epidermal restructuring throughout the study duration. Subject assessments reflected positive product tolerability and positive perception across a broad range of efficacy attributes through 12 weeks of usage. Conclusion: The results verified the ability of a multi-modal plant and enzymatically derived growth factor-based product to achieve skin rejuvenation improvements by stimulating dermal ECM and fibrous tissue regeneration to reduce fine lines and coarse wrinkles, and improve skin firmness and elasticity, while restoring skin to a properly hydrated state. J Drugs Dermatol. 2019;18(3):290-295.