Rice protein residue (RPR) and corn germ meal (CGM) are industrial by-products that are commonly applied as animal feed with low economic benefits. In order to develop a new approach for the resource utilization of grain protein residue, this study converted grain protein residue into edible mushroom protein through solid-state fermentation (SSF). To increase the biological efficiency of biotransformation, this study used Box Behnken design, combined with single factor experiments and response surface methodology, to optimize the SSF process parameters of edible mushroom mycelium. Optimal fermentation conditions were established considering both protein content and operational feasibility: RPR to CGM ratio of 4:1, utilizing the Pleurotus ostreatus strain, a fermentation duration of 14.5 days, a solid-to-liquid ratio of 1:0.8, and a loading capacity of 65.59 g. Fermentation under these optimized conditions yielded 73.34 g of protein per 100 g of RPR/CGM blend, which is 98.71% of the predicted value and represents a 1.28-fold increase from the initial protein content of 56.96 g/100 g. The amino acid evaluation results showed that the total amino acid content of the fermented protein residue increased by 12.88%, with a significant increase in the concentrations of glutamic acid and aspartic acid, which increased by 19.53% and 24.27%, respectively. In addition, the amino acid ratio coefficient score (SRC) and nutritional index (NI) were slightly higher, indicating a more balanced proportion of essential amino acids after fermentation. Additional research on the physicochemical properties of the protein residue post-fermentation revealed that the emulsifying capacity improved by 3.5% compared to the non-fermented sample. Edible mushrooms are a promising method for converting RPR and CGM into high-protein raw materials.