Teff is a tropical cereal native to Ethiopia that is attracting attention due to its nutritional excellence and being gluten-free. The phenolic content of this cereal is higher than other grains including wheat, rice, oats, sorghum, corn, quinoa and amaranth. In this study, the extraction of phenolic compounds from teff grains was evaluated using a Simplex-centroid mixture design with water, ethanol and methanol. The solid-liquid extraction was carried out by high energy dispersion (UT) and ultrasound (US). The total phenolic content (TPC) was used to obtain the response surfaces and to optimize the solvent composition for extraction. After optimization and validation, the total flavonoid content (TFC) and the antioxidant capacity (estimated by the methods of DPPH, ABTS and FRAP) of the extracts were also evaluated. The highest TPC contents were obtained using extraction mixtures containing 51% of water, 40% of ethanol and 9% of methanol (208.24 mg GAE.100 g-1) by UT and 49% of water, 26% of ethanol and 25% of methanol by US (213.11 mg GAE.100 g-1). There were not significant differences (p > 0.05) between the methods used for TPC extraction and the percentage of methanol required in UT is lower (9%) than in US (25%). The experimental results were well correlated with the mathematical model confirming its quality for prediction. The TFC (106.03 mg CE.100 g-1) and the antioxidant capacity were significantly higher in extracts extracted by US. Simplex-centroid design proved to be an efficient tool for the optimization of the extraction of phenolics from teff grains. As observed, both methods studied were efficient, but the results suggest that UT is the better technique, because, although the extraction time is higher, a lower proportion of methanol is required which represents lower cost and lower health and environmental risks.