Ganoderma lucidum is a famous medicinal mushroom that is rich in antioxidants. The content of antioxidant components of grains can be effectively improved by G. lucidum as the fermenting strain. Optimization of the solid-state fermentation medium and optimization of the fermentation conditions were studied. The optimal fermentation substrate combination of G. lucidum TS (GL-TS) was 46.79% buckwheat, 53.21% rice; the optimal fermentation substrate combination of G. lucidum Am (GL-Am) was 4.17% soybean, 95.83% rice. The optimal fermentation conditions of GL-TS and GL-Am were as follows: inoculum amounts of 4.5% and 7.5%, temperatures of 30°C and 32°C, medium moisture content of 70% for both media, material granularities of 0.212-0.355 mm and 0.500-0.710 mm, and optimal fermentation time of 12.0 d and 10.5 d, respectively. Results of the analysis of antioxidant components in the fermentation substrates indicated that the antioxidant components were rich in antioxidant varieties and high in content. The contents of the antioxidant components (triterpenoids, total polyphenols, reducing sugars, anthocyanins, superoxide dismutase, glutathione, vitamin C, and vitamin E) in the full-fermentation substrates were greater than those in the nonfennentation substrates (except for flavonoids in the full-fermentation substrates, which were less than in the nonfennentation substrates). Glutathione was the major antioxidant component in the fermentation substrates, and the glutathione content was the highest. Therefore, the fermentation substrates of G. lucidum can be used to make antioxidant foods. This research contributes to the foundation for developing antioxidant foods based on G. lucidum.