Podophyllum rhexandrum (Indian May Apple) was successfully cultivated-in a 3 L stirred tank bioreactor under low shear conditions in batch and fed-batch modes of operation. A statistically, optimized culture medium was used for the batch cultivation of Podophyllum hexandrum. Under optimum culture conditions of P. hexandrum, the batch culture showed a growth-associated product formation with, a maximum biomass of 21.4 g/L dry cell weight (DCW) basis and a podophyllotoxin production of 13.8 mg/L in 26 d. A mathematical model was developed to design the nutrient feeding strategies for a fed-batch cultivation to prolong the productive log phase of cultivation. The fed-batch, cultivation was able to enhance the biomass and podophyllotoxin accumulation to 48, g/L (DCW basis) and 43.2 mg/L, respectively, in 60 d. The volumetric productivity of podophyllotoxin in fed-batch cultivation was found to be 0.72 mg/(L. d) as opposed to 0.53 mg/(L d) in batch cultivation under optimized culture conditions.