Rapeseed meal (RM) is produced in large quantities as a byproduct of oil extraction from rapeseeds. However, the efficient utilization of RM as animal feed is limited by its low metabolizable energy, poor palatability, and high levels of fiber and anti-nutritional components. Here, we investigate the potential of enriching RM with single-cell protein through fermentation with conventional and unconventional yeasts. The process of simultaneous saccharification and fermentation improved the parameters of the waste biomass, especially the protein content, while reducing the amount of crude fiber and enhancing the biotransformation of isoflavone compounds present in the waste. Fermentation yielded the highest protein gain for the Saccharomyces cerevisiae Ethanol Red strain (ΔN = 2.38%) at a biomass load of 12.5 g and for Scheffersomyces stipitis (ΔN = 2.34%) at an enzyme dose of 0.125 mL/10 g DM. The crude fiber content (CF) was reduced by 2.55−7.18%. The simultaneous saccharification and fermentation (SSF) process resulted in the conversion of isoflavones to forms with fewer adverse effects and a lower estrogenic activity. The results show the potential of using RM as a substrate for making a nutritionally improved feed components.