Distiller’s dried grains with solubles (DDGS) contain many growth nutrients at similar or higher levels compared with media components used in cellulose fermentation for biofuels (ethanol and hydrogen) and organic acids productions. This study investigates the potential to replace expensive and reagent grade growth media (1191) components used in lab scale cellulose fermentation process for ethanol, H2, and organic acids production with DDGS as the major component of the culture medium. Batch cultures of Clostridium thermocellum were cultivated on α-cellulose (2 g/l) using two different concentrations (2 and 5 g/l) of DDGS in sodium-potassium phosphate buffer solution. Cultures of C. thermocellum in 1191 medium with α-cellulose were cultivated simultaneously. Controls consisting of DDGS plus buffer only were used to determine the extent of α-cellulose utilization as substrate. Standard cultures with added DDGS (2 and 5 g/l) were also evaluated to determine the effect of DDGS on product synthesis. By 24 hours, ethanol production in cultures containing 5 g/l DDGS in buffer only plus α-cellulose was equivalent to that of cultures containing 1191 plus α-cellulose, but H2 accumulation in cultures containing 2 or 5 g/l DDGS in buffer only was 58% and 68%, respectively, of the H2 produced by cultures containing 1191 medium plus α-cellulose. DDGS has some buffering capacity, less severe drops in pH were observed in cultures containing DDGS. Although H2 production in cultures containing DDGS is reduced compared to cultures containing 1191 medium, DDGS has potential to replace expensive lab-grade media components with respect to ethanol production.