Abstract Diabetes mellitus is a major global health problem. Various plant extracts have proven antidiabetic activity and are considered as promising substitution for antidiabetic drugs. The antihyperglycemic effect of 16 plants and 4 algae, commonly used in Egypt for the treatment of diabetes mellitus, was investigated. A diabetes model was induced by intraperitoneal injection of nicotinamide (120 mg/kg body weight [b.wt.]), then streptozotocin (200 mg/kg b.wt.) after 15 min. Hydroethanolic extracts (80%) of the plants and algae under investigation were prepared. The extracts were orally administered to nicotinamide-streptozotocin-induced diabetic mice by a gastric tube at doses 10 or 50 mg/kg b.wt. for 1 week. The antidiabetic activity was assessed by detection of serum glucose concentrations at the fasting state and after 2 h of oral glucose loading (4.2 mg/kg b.wt.). Extracts prepared from Cassia acutifolia, Fraxinus ornus, Salix aegyptiaca, Cichorium intybus, and Eucalyptus globulus showed the highest antihyperglycemic activity among the tested plants. Extracts prepared from Sonchus oleraceus, Bougainvillea spectabilis (leaves), Plantago psyllium (seeds), Morus nigra (leaves), and Serena repens (fruits) were found to have antihyperglycemic potentials. Extracts prepared from Caulerpa lentillifera and Spirulina versicolor showed the most potent antihyperglycemic activity among the tested algae. However, some of the tested plants have insulinotropic effects, all assessed algae have not. Identification of lead compounds from these plants and algae for novel antidiabetic drug development is recommended.