Background: Aquatic plants play a crucial role in nature-based wastewater treatment and provide a promising substrate for renewable energy production using anaerobic digestion (AD) technology. This study aimed to examine the contaminant removal from AD effluent by water lettuce (WL) and produce biogas from WL biomass co-digested with pig dung (PD) in a farm-scale biogas digester. Methods: The first experiment used styrofoam boxes containing husbandry AD effluent. WLs were initially arranged in 50%, 25%, 12.5%, and 0% surface coverage. Each treatment was conducted in five replicates under natural conditions. In the second experiment, WL biomass was co-digested with PD into an existing anaerobic digester to examine biogas production on a farm scale. Results: Over 30 days, the treatment efficiency of TSS, BOD5, COD, TKN, and TP in the effluent was 93.75–97.66%, 76.63–82.56%, 76.78–82.89%, 61.75–63.75%, and 89.00–89.57%, respectively. Higher WL coverage increased the pollutant elimination potential. The WL biomass doubled after 12 days for all treatments. In the farm-scale biogas production, the biogas yield varied between 190.6 and 292.9 L kg VS−1 added. The methane content reached over 54%. Conclusions: WL removed AD effluent nutrients effectively through a phytoremediation system and generated significant biomass for renewable energy production in a farm-scale model