Hybrid lecithin-chitosan (LC) ethosomes were developed for maximizing encapsulation efficiency and release of Kaempferol (KMP) in controlled effect for topical delivery. The hybrid lecithin–chitosan offers the benefits of both components: enhanced lipophilicity and mucoadhesive, respectively. In this work, hybrid lecithin-chitosan KMP ethosomes (Eth) were prepared via a cold technique and assesses its physicochemical properties, in vitro and in vivo studies. The synthesized LC-Eth-vesicles of KMP reported vesicle size of 186.8 nm with polydispersity index of 0.285 and 31.9 mV of zeta-potential. The encapsulation efficiency was 96.2 %. In vitro drug release profile has shown prolonged release of KMP in a controlled manner over a period of 24 h. Around 80.3 % KMP was released from LC-KMP-Eth gel while only 46.9 % of KMP was released from the plain KMP-gel in 24 h. The release kinetic investigation the release of KMP followed the “Korsmeyer-Peppas model” with Fickian-diffusion mechanism. The LC-KMP-Eth has shown increased antimicrobial activity as compared plain KMP gel against multiple strains of MRSA. The histopathological analysis of skin samples revealed an increased re-epithelization with reduced wound ulcer which was also observed by the visual examination of the skin conditions. The in vivo results on Wistar albino rat models demonstrated superior wound closure efficacy of LC-KMP-Eth gel as compared to plain KMP gel. Around 2-fold overall increased pharmacokinetic parameters of KMP from LC-KMP-Eth gel after topical application, displayed a higher concentration of KMP in rat plasma, reveling a potent effect at the wound site and the gel also provide the moist environment and influencing cell adhesion, thus stimulating restorative action in diabetic foot ulcers.