The floating system is a successful strategy for producing baby leaf vegetables. Moreover, compost from agricultural and agri-food industry wastes is an alternative to peat that can be used as a component of growing media in this cultivation system. In this study, we experimented with three composts containing tomato (Solanum lycopersicum L.), leek (Allium porrum L.), grape (Vitis vinifera L.), and/or olive (Olea europaea L.) mill cake residues, which were used as the main component (75/25 volume/volume) of three growing media (GM1, GM2 and GM3) to evaluate their effect on the growth and quality of red baby leaf lettuce (Lactuca sativa L.). We used a commercial peat substrate as a control treatment (100% volume) and in mixtures (25% volume) with the composts. The plants were cultivated over two growing cycles, in spring and summer, and harvested twice in each cycle when the plants had four to five leaves. We found that the percentage of seed germination was significantly higher in plants grown in peat than in those grown in compost growing media. The yield was affected by the growing media in the summer cycle, and we obtained the highest value with GM1. Furthermore, the second cut was more productive than the first one for all the growing media in both cycles. The lettuce quality was also affected by the growing media. In general, the total phenolic content and antioxidant capacity in the leaves was higher in plants grown in the compost growing media, particularly in the second cut, but the nitrate content in the leaves was greater in some of the compost treatments compared with the peat treatment. In addition, an in vitro suppressive activity study demonstrated that the interaction between different fungi and bacteria observed through metagenomics analysis could contribute to the effectiveness of the compost in controlling Pythium irregulare. The use of compost as a component of the growing media in the production of baby leaf vegetables in a floating system does not only favor the crop yield and product quality, but also shows suppressive effects against P. irregulare.