Duckweed (Lemna) is a possible solution for the treatment of aqueous waste streams and the simultaneous provision of protein-rich biomass. Nitrification-Denitrification effluent (NDNE) from pig manure treatment has been previously used as a growing medium for duckweed. This study investigated the use of a continuous duckweed cultivation system to treat NDNE as a stand-alone technology. For this purpose, a system with a continuous supply of waste streams from the pig manure treatment, continuous biomass production, and continuous discharge that meets the legal standards in Flanders (Belgium) was simulated for a 175-day growing season. In this simulation, salt accumulation was taken into account. To prevent accumulating salts from reaching a toxic concentration and consequently inhibiting growth, the cultivation system must be buffered, which can be achieved by altering the depth of the system. To determine the minimum depth of such a system, a tray experiment was set up. For that, salt accumulation data obtained from previous research were used for simulating systems with different pond depths. It was found that a depth of at least 1 m is needed to prevent a significant relative growth inhibition at the end of the growing season compared to the start. This implies a high water consumption (5–10 times more than maize). As a response, a second cultivation system was investigated for the use of more concentrated NDNE. For this purpose, salt tolerance experiments were conducted on synthetic and biological media. Surprisingly, it was observed that duckweed grows better on diluted NDNE (to 75% NDNE, or EC of 8 mS/cm) than on a synthetic medium (EC of 1.5 mS/cm), indicating the potential of such a system.