Posidonia [Posidonia oceanica (L.) Delile] is a marine phanerogam endemic of the Mediterranean Sea that grows all along the coast forming extensive underwater meadows. Senescent posidonia leaves, together with fibers (residues of rhizomes and decomposed leaves), periodically accumulate along Mediterranean beaches, covering vast areas of coast. Removal and disposal of these large volumes of plant biomasses represent a high cost for local administrations. Therefore, in this experiment, beached residues of posidonia were composted with olive pruning and green wastes with the objective to assess the efficacy of posidonia-based compost (63% on a volume basis) as a peat replacement. The compost was then mixed with a peat-based commercial substrate at rates of 0% (C0, pure peat-based commercial substrate tested as control), 25% (C25), 50% (C50), 75% (C75), and 100% (C100, pure posidonia-based compost) v/v. Mixtures were used as growing media to produce lettuce seedlings for transplant. Two lettuce cultivars (8511RZ and Satine) were tested. Main physical and chemical properties of the five growing media, shoot and root fresh and dry weight, leaf area, root morphology, and elemental leaf tissue composition were studied. Growing media containing posidonia-based compost, C25 and C50 in particular, showed good physical properties. Increasing compost proportions in the mixtures resulted in enhanced: 1) availability of macro- and micronutrients in the growing media; and 2) overall growth parameters of lettuce seedlings, in particular for the cultivar Satine. In conclusion, posidonia-based compost shows a considerable potential as a peat substitute in horticultural substrates; posidonia residues are a low-cost renewable material. In growing media for lettuce seedlings production, posidonia-based compost could be used as a complement to peat at a rate of 25% or 50% to obtain optimal physical properties and to limit the negative effects of high B content, which are typical of posidonia residues.