The intracellular triterpene yield from <i>Ganoderma atrum</i> was enhanced by optimization based on single-factor experiments, Plackett-Burman experimental design (PBED) and response surface methodology (RSM) under liquid fermentation conditions. The optimal medium composition (g·L<sup>-1</sup>) was glucose (46.0), bean cake powder (30.2), KH<sub>2</sub>PO<sub>4</sub> (2.0), CaCl<sub>2</sub> (3.0), MgSO<sub>4</sub> (1.5), FeSO<sub>4</sub> (0.2), and pH 6.0. Under the optimal conditions, the highest triterpene yield of 0.527 g·L<sup>-1</sup> was obtained, which was 4.705-fold higher than before optimization. The fermented powder that was collected from the optimal medium was subjected to simulated gastrointestinal digestion, with differences resulting from extraction in different digestive juices (purified water, simulated gastric digestive juice, simulated gastrointestinal digestive juice). The content of triterpenes and polysaccharides increased, except for total phenol content. In terms of the antioxidant activity, the 1,1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH<sup>+</sup>⋅) scavenging activity gradually decreased whereas the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS<sup>+</sup>⋅) scavenging activity first decreased and then increased. In terms of enzyme viability, the activity of α-amylase (α-AL) and α-glucosidase (α-GC) in the digestive juices decreased dramatically. The main bioactive components of <i>G. atrum</i> and their bioactivity in digestive juices were evaluated, providing a reference for the effective use of fermented power from <i>G. atrum</i>.