Large amounts of organic waste are produced worldwide. This work aims to evaluate the influence of organic fertilizers, onion peel flour (OPF) and fruit and vegetable flour (FVF) on lettuce cultivation. Lettuce seeds were planted in pure soil (P), P with 10% OPF, and P with 3% FVF. Soil and lettuce leaves were analyzed. The addition of OPF and FVF improved soil quality but only in the soil with FVF was there significant lettuce growth and increase of antioxidant activity: Folin (8.89 mg EAG/g FM), FRAP (1.31 mg Fe2+/g FM), ABTS (4.09 mg TEAC/g−1 FM) and ORAC (0.52 mg TEac/g−1 FM). The present results show an improvement in lettuce nutritional quality and the potential of FVF as an organic fertilizer.