Ethoxylated aliphatic surfactants belonging to the Genapol and Tergitol series were assessed as extraction systems of isoflavones. They showed good extraction properties when compared with different solvents, the Genapol X-080 exhibiting the best performance. Available commercial isoflavone pills were used, as a starting simple matrix, to determine the parameters that affect the extraction procedure. The temperature and the surfactant concentration showed to be factors that favored significantly the extraction performance. The application of optimized variables (Genapol X-080 11% m/m, pH 4.5; extraction temperature of 54 °C and extraction time of 60 min) on soybean flour (natural) allowed extracting 3.237 ± 0.173 mg of isoflavone per gram of treated flour. This result was three times what it was for methanol under identical conditions. Extraction with these micellar systems represents a sustainable alternative methodology for industrial purposes due to its low cost, biodegradability, non-toxicity and easy scaling up.