Phytomedicine has moved beyond being seen only as a folklore remedy and has become an important part of modern therapeutics. Aloe-emodin (AE), a phytoconstituents present in Aloe, is a naturally occurring anthraquinone, exhibits notable anti-inflammatory, antimicrobial, and wound-healing properties. However, its clinical potential is limited by poor aqueous solubility and inadequate skin permeability. To overcome these challenges, an AE-loaded gel (AMEG) was developed to enhance topical delivery and therapeutic efficacy in diabetic wound management. The formulation was optimized using a D-optimal mixture design, selecting Capryol 90 as the oil phase, Labrasol and Tween 80 as surfactants, and Transcutol P as the co-surfactant. A stable gel matrix was formed by incorporating konjac glucomannan (KGM) and carbopol 940, improving skin adherence and drug retention. The optimized AMEG demonstrated nanoscale droplet size, high zeta potential, and excellent clarity. In vitro and ex vivo studies confirmed sustained drug release and enhanced transdermal penetration. In vivo application in diabetic rats significantly accelerated wound healing, accompanied by modulation of key inflammatory and oxidative markers, including IL-1, IL-6, NF-kB, TNF-α, MDA, and AGEs. Histopathological assessments revealed full re-epithelialization and organized collagen deposition. The combined effect of AE and KGM underscores the potential of AMEG as a promising, non-invasive therapeutic approach for diabetic wound care, leveraging the advantages of herbal compounds in enhancing healing and reducing inflammation.