The potential of utilizing dried sweet sorghum stalks as raw material for anaerobic digestion has been evaluated. Two different treatments were tested, a mild thermal and an enzymatic, alone or in combination. Thermal pretreatment was found to decrease the methane yields, whereas one-step enzymatic treatment resulted in a significant increase of 15.1% comparing to the untreated sweet sorghum. Subsequently, in order to increase the total methane production, the combined effect of enzyme load and I/S on methane yields from sweet sorghum was evaluated by employing response surface methodology. The obtained model showed that the maximum methane yield that could be achieved is 296 mL CH4/g VS at I/S ratio of 0.35 with the addition of 11.12 FPU/g sweet sorghum.