© 2021, Romanian Society for Pharmaceutical Sciences. All rights reserved.The aim of the study was to evaluate the total phenolic content, in vitro antidiabetic and antioxidant potential of marine organisms collected from Mediterranean coast. Methanol extracts of one soft coral (Eunicella singularis) and twelve sponge species (Agelas oroides, Aplysina aerophoba, Axinella cannabina, A. polypoides, Cliona viridis, Dictyonella incisa, Dysidea avara, Ircinia incisa, I. oros, I. variabilis, Petrosia ficiformis, Sarcotragus spinulosa) were investigated for their enzyme inhibitory activities, total phenolic content, total antioxidant capacity, ferric reducing antioxidant power, metal chelating and radical scavenging activities. Dysidea avara was found to be the most active extract on α-glucosidase enzyme (94.66-4.87% for 3000-100 µg/mL). Therefore, α-glucosidase inhibitory activity of its major compounds avarol and avarone was tested and found to be 86.18 ± 1.76% and 78.94 ± 1.38% at 10 µM respectively. The present study indicated that the sponge Dysidea avara can be evaluated as a new natural source in the treatment of diabetes mellitus.