Lettuce (Lactuca sativa L) is a leafy vegetable containing an immense variety of minerals, vitamins and health-promoting secondary metabolites which are required for normal functioning of human body and health. Anaerobic digestate contains proportionately higher mineralized nutrients particularly ammonium-N (NH4⁺ -N) compared to undigested materials, and therefore has the potential to be used as a mineral nutrient source in soil based and soilless culture. A pilot study was conducted at St. Davids dairy farm site to investigate the effects of anaerobic dairy digestate (DD), inorganic nutrient solution (NS) and combine application of DD and NS on the growth, yield and quality indices of lettuce varieties in hydroponics under controlled environment conditions. Results showed that NS produced significantly higher leaf area (LA), chlorophyll content, root dry weight, yield, minerals and vitamins concentration of lettuce, compared to DD solution which produced lower LA, chlorophyll contents, yield and higher concentration of phenolics (chicoric acid, chlorogenic acid, luteoline, quercitin-3-b-d-gluconide, quercitin-3-glucoside and quercitin-b-malonyl) and antioxidants. Romaine lettuce showed superior performance and produced higher LA, chlorophyll contents, root dry weight, yield, minerals, vitamins, total phenolics, total antioxidants and polyphenols than Newham. It can be concluded that DD can be used as an organic fertilizer/nutrient source in hydroponics to enhance phenolics and antioxidants of lettuce without significant reduction in yield. Further research is needed to reduce Ammonium-N/Nitrate (NH4⁺/NO3⁻) in DD without dilution to avoid phytotoxic effects of NH4⁺ and loss of other macro and micro nutrient , and to establish the utilization of DD as a sole fertilizer source in hydroponic system