Abstarct: Ganoderma lucidum with high curative properties has been used worldwide. This fungi is of two vital components, ganoderic acid and polysaccharide. In the present research, the effect of chemical conditions of media were examined on Ganoderam growth and secondary mextabolisms ( polysaccharide and ganoderic acids) to determine the key substrates which had the most positive impact on the fungi productions. The experimentations were conducted in two sections. First, One Factor at Time was applied to examine five carbon sources (Glucose syrup, Glucose powder, Fructose syrup, Wheat starch and Corn starch), five nitrogen sources (Whey powder, Soy powder, Corn Steep Liquor syrup, Yeast extract and Meat Peptone), seven pH (5, 5.5, 6, 6.5, 7, 7.5 and 8), three concentration (0.1, 0.05 and 0.01 g/L ) of TiO2 and MgO nanoparticles and four levels of vitamin Pyridoxine (B6) (10, 20, 100 and 300 μL/L). Then, the best substrates for secondary mextabolisms and growth were determined. In the second section, response surface method was served to optimize the ganodric acid and polysaccharide productions through the key substrates determined by One Factor at Time. The results indicated that Glucose syrup, Whey powder and initial pH 5, 0.1 g/L TiO2 nanoparticles, 0.05 g/L MgO nanoparticels and100 μL/L B6 had the highest positive effect on Ganoderma growth. One Factor at Time method indicated that the medium containing Wheat starch, Whey protein, initial pH 6.5, 0.01 g/L MgO nanoparticels and 20 μL/L medium B6 supported the highest content of polysaccharides. RSM revealed that medium containing 37.5 g/L Wheat starch and 20 g/L whey powder was by far the best substrates which stimulated the highest content of polysaccharide. One Factor at Time showed that Glucose syrup, Yeast extract and initial pH 6.5, 0.05 g/L TiO2 and MgO, 100 μL/L B6 exerted a high influence on ganoderic acid. RSM method showed that 50 g/L Glucose syrup and 30 g/L CSL induced the highest quantity of ganoderic acid.