Monacolin K and yellow pigment, produced by Monascus sp., have each been proven to be beneficial compounds as antihypercholesterolemic and anti-inflammation agents, respectively. However, citrinin, a human toxic substance, was also synthesized in this fungus. In this research, solidstate fermentation of M. purpureus TISTR 3541 was optimized by statistical methodology to obtain a high production of monacolin K and yellow pigment along with a low level of citrinin. Fractional factorial design was applied in this study to identify the significant factors. Among the 13 variables, five parameters (i.e., glycerol, methionine, sodium nitrate, cultivation time, and temperature) influencing monacolin K, yellow pigment, and citrinin production were identified. A central composite design was further employed to investigate the optimum level of these five factors. The maximum production of monacolin K and yellow pigment of 5,900 mg/kg and 1,700 units/g, respectively, and the minimum citrinin concentration of 0.26 mg/kg were achieved in the medium containing 2% glycerol, 0.14% methionine, and 0.01% sodium nitrate at 25oC for 16 days of cultivation. The yields of monacolin K and yellow pigment were about 3 and 1.5 times higher than the basal medium, respectively, whereas citrinin was dramatically reduced by 36 times.