Cinnamomum verum, Origanum majorana, and Origanum vulgare have been used in traditional medicine for a long time to treat diabetes because of their promising therapeutic effects. The combination of these plants (COO) was tested to improve their efficacy using selenium nanoparticles (Se-COO-NPs) and gum Arabic (GA) as stabilizers for sustained release. Phenolic compounds of plants were identified using liquid chromatography–mass spectrometry (LC–MS/MS). GA-Se-COO-NPs were characterized by spectroscopic and microscopic methods and evaluated in diabetic zebrafish. The ultraviolet spectrum was assessed to confirm the formation of plasmon resonance at 267 nm. The obtained particle size of selenium nanospheres was 65.76 nm. They were maintained in a stable form for 5 months at 4 °C. Transmission electron microscopy (TEM) images demonstrated the presence of individual spherical nanoparticles. Fourier transform infrared spectroscopy (FT-IR) showed the interaction between COO extract and selenium, exhibiting good entrapment efficiency (87%). The elemental analysis of COO extract and GA-COO-SeNPs confirmed that NPs were obtained. The zebrafish were exposed to a high glucose concentration for two weeks, and type 2 diabetes and oxidative stress responses were induced. In diabetic zebrafish, treatment with NPs showed antilipidemic and hypoglycemic effects, high survivability, and reduced levels of glucose, reactive oxygen species (ROS), and lipids in the blood. This group this had a higher survivorship rate than the diabetic control. The results demonstrated that GA-Se-COO-NPs have high antidiabetic potential, most likely because of the synergic effects of phenolic compounds and Se nanoparticles.