Cordyceps cicadae is a well-known traditional Chinese medicine for treating palpitations and eye diseases. It contains several bioactive compounds such as adenosine, N6-(2-hydroxyethyl)-adenosine (HEA), and polysaccharide. Those bioactive compounds have been reported to perform anti-oxidation and anti-inflammatory properties and provide renal protection. In this study, we researched different fermentation conditions in order to enhance the biomass, adenosine, HEA, and polysaccharide productions of C. cicadae NTTU 868. Solid fermentation was carried out with different grain substrates (barley, oat, rice and wheat). Various submerged fermentation scales were used to produce the C. cicadae NTTU 868 mycelium. The results of solid fermentation revealed that C. cicadae NTTU 868 produced higher adenosine and HEA concentrations in oat rather than in other substrates. C. cicadae NTTU 868 mycelium had obtained the highest concentrations of adenosine and HEA on Day 2 as using the small-scale submerged fermentation. Furthermore, potato dextrose broth with extra 0.2% of yeast extract was able to result in higher HEA concentration. In conclusion, using submerged fermentation to culture C. cicadae NTTU 868 resulted in more efficient adenosine, HEA, and polysaccharide productions than using solid-fermentation, especially when 0.2% of yeast extract was used in the PDB. Importantly, this can be easily scaled-up in the fermentation industry.