Food waste liquid anaerobic digestate (FWLAD) has strong potential as an organic fertilizer due to its nutrient-rich composition. However, organic nutrient solutions often have lower dissolved oxygen (DO) levels than inorganic ones, which may limit oxygen availability in the root zone, restricting nutrient uptake and plant growth. This study examines whether increasing perlite content in a soilless substrate and aerating the nutrient solution can enhance root-zone oxygen availability and improve lettuce (Lactuca sativa 'Muir') growth when cultivated with FWLAD. Lettuce seeds were sown in a 128-cell plug tray filled with a peat-based growing mix blended with perlite at 100%:0%, 70%:30%, and 40%:60% (v:v). Increasing perlite content from 0% to 60% increased substrate porosity from 47% to 56%, while air space remained between 30% and 33%. One week after sowing, seedlings were sub-irrigated with four nutrient solutions prepared from either crude or nitrified FWLAD at an electrical conductivity (EC) of 2 dS·m-1, each under aerated and non-aerated conditions. Control nutrient solutions were prepared using inorganic fertilizer at 2 dS/m EC. Lettuce seedlings were grown indoors for three weeks at the air temperature of 24°C with a photosynthetic photon flux density of 210 µmol·m-2·s-1 under an 18-hour photoperiod. Regardless of nutrient solution type, increasing perlite from 0% to 60% had little to no effects or decreased leaf number (by 7-13%), leaf area (by 13-26%), and shoot fresh mass (by 10-42%). DO levels remained below 1.5 ppm in non-aerated crude or nitrified FWLAD solutions, while aerated solutions and inorganic fertilizer treatments maintained DO above 6 ppm. Aerating the nutrient solution with crude FWLAD decreased total leaf number (by 4-17%), total leaf area (by 28-45%), and shoot fresh mass (by 37-44%) across all substrate conditions, whereas aeration with nitrified FWLAD increased these parameters by 22-35%, 174-343%, and 138-325%, respectively. At each substrate condition, lettuce seedlings grown with inorganic fertilizer had the highest leaf number, leaf area, and shoot fresh mass. These results suggest that increasing perlite content did not enhance lettuce growth under FWLAD. Aeration improved growth with nitrified FWLAD but reduced it with crude FWLAD. Across all conditions, inorganic fertilizer resulted in the highest growth, suggesting that factors beyond oxygen availability may limit the effectiveness of FWLAD as a nutrient source.