Abstract: The Monascus anka MA-25 with high yield of γ-aminobutyric acid (GABA) and the Monascus. purpureus MP-19 producing lipid-reduction pigment were selected as the research strains. The best culture conditions of red yeast rice to increase the GABA yield of MA-25 were screened through single factor, Plackett-Burman experimental design and Box-Behnken response surface experimental design. Simultaneously, the amino acid with the best inhibitory effect on α-amylase were screened out for MP-19. Finally, the best culture condition of combined fermentation of MA-25 and MP-19 was selected by orthogonal experiment to achieve the goal that the metabolites not only high GABA production but also the best inhibition rate of dietary related enzymes. The results showed that the optimized culture conditions of MA-25 were glutamate 1.18%, glucose maltose 1.16% and pH6.08% and the highest yield of GABA in red yeast rice of MA-25 was 5.608 mg·g^-1, which was 20.58% higher than that before optimization (4.651 mg·g^-1). Besides, the optimumα-amylase-reduction amino acid of MP-19 was L-tryptophan (L-Trp). Finally, considering the maximization of lipid reduction ability, the optimum condition of co-fermentation of MA-25 and MP-19 was that:Rice 20%, ammonium sulfate 1.0%, initial pH6.5, glucose maltose 0.50%, glutamic acid 1.50%. L-Trp 1.0%, NaH₂PO₄ 1.0%, water 57.0%, and the GABA production was 5.400 mg·g^-1, α-amylase inhibition rate was 57.15%, protease inhibition rate was 28.14%, lipase inhibition rate was 29.67%.