Diabetic skin ulcer is one of the most severe complications in diabetes, however, current therapeutic approaches are not effective enough. Agents modulating oxidative stress, inflammation, and angiogenesis are quite promising for alleviation of diabetic skin ulcers. In this study, a novel Sargassum kjellmanianum-derived polysaccharide (SARP) was prepared. SARP was an alginate with Mw of 45.4 kDa, consisting of 76.56% mannuronic acid, 18.89% guluronic acid, and 4.55% glucuronic acid. SARP could attenuate oxidative stress-induced cell damage via activating nuclear factor erythroid 2-related factor 2 (Nrf2). SARP also promoted the migration and tube formation of HUVECs, which was related to the increased vascular endothelial growth factor (VEGF) expression. In diabetic wound model, SARP (iv, 200 mg/kg) administration increased angiogenesis, alleviated oxidative stress, ameliorated diabetes-related aberrations, and thereby accelerated diabetic wound healing. These findings identified SARP had potential to be developed as a drug candidate for diabetic skin ulcers.