Spirodela polyrhiza (L.) has been known as greater duckweed or great duckmeat. It is native inhabited in Korea. It is considered as a rich source of primary metabolites including protein, carbohydrates, and fats. Thus, it is considered as an alternative food source for the future. In addition, it has a strong phytoremediation capacity to remove various environmental pollutants, especially inorganic elements and pesticides. With a variety of duckweed’s application, there is an urgent need to develop a cultivation method for a sustainable supply of S. polyrhiza. In this study, an indoor vertical farm has been introduced to optimize duckweed cultivation. Indoor cultivated S. polyrhiza showed about 2-fold higher fresh weight than outdoor cultivated duckweed. Contents of inorganic elements were also significantly reduced in indoor cultivated S. polyrhiza. Especially, lead (Pb), cadmium (Cd), and arsenic (As) were approximately 10-fold decreased in indoor cultivated duckweed. On the other hand, contents of proteins and fats were significantly increased in indoor cultivated S. polyrhiza, while carbohydrates were found more in outdoor cultivated S. polyrhiza. Increasing N content in a homemade nutrition solution also enhanced fresh and dried weights of S. polyrhiza by about 1.8-fold in comparison with other commercial nutrition solutions. Proliferation rate (%) was doubled every 24 hours in this indoor vertical farm, indicating the accomplishment of a sustainable supply for S. polyrhiza. Further studies need to be undertaken to cultivate other duckweeds such as Wolffia arrhiza and Lemna minor using the same indoor farming system.