Crop-specific nutrient solution and suitable growing media mixtures are necessary in hydroponic system to improve the yield of vegetables. Therefore, an experiment was conducted to specify the required amount of nutrient solution and ecofriendly mixtures of growing substrates of a hydroponic bitter gourd. Treatments consisted two factors, viz., four different types of growing substrate (M1 = 60% rice husk + 30% coconut coir + 10% vermicompost, M2 = 60% coconut coir + 30% khoa + 10% vermicompost, M3 = 60% sawdust + 30% khoa + 10% vermicompost, and M4 = 60% ash + 30% khoa + 10% vermicompost) and three different composition of nutrient solutions [N1 = full strength , N2 = full strength , and N3 = ½ strength ]. Photosynthetic responses and its related parameters, namely, stomatal conductance (gs), transpiration (E), and photosynthetic rate (PN) were significantly affected by nutrient solution composition and growing substrate mixtures. Results revealed that the leaf gas exchange parameters, yield contributing characters, and biochemical parameters showed that full strength of nutrient solution application was better in a growing mixture of 60% rice husk + 30% coconut coir + 10% vermicompost in soilless culture for obtaining high yield and high quality of bitter gourd.