Soil acidity poses a challenge to crop production by limiting the availability of nutrients for plants. The aim of this study was to assess the efficacy of a natural waste-based fertilizer composed of Mytilus chilensis seashells, coffee bean wastes, banana peels, and wood ashes on lettuce growth and physiological quality. The seashells were used with organic matter (W-OM), without organic matter (Wo-OM), and a mixture of equal parts of W-OM and Wo-OM (50:50). The coffee bean wastes, banana peels, and wood ashes were used as ingredients. The soil pH, chlorophyll index in the lettuce leaves, and nitrogen level (in the soil and leaf) were measured for a period of 66 days. Vitamin C content in the harvested leaves was measured. The W-OM fertilizer allowed for an increase the soil pH from less than 6.5 to 7.0±0.5. The nitrogen provided by the coffee bean waste was partially available to the plant root, which decreased the chlorophyll index in the lettuce leaves. The studied fertilizer (W-OM, Wo-OM, and 50:50) allowed to increase of vitamin C content in the lettuce leaves. In conclusion, the natural waste-based fertilizer showed a promising effect in alleviating soil acidity and enhancing the nutritional quality of lettuce plants.