Worldwide, there is an increase in acreage dedicated to the competitive production of fruits, vegetables, flowers, and palms crops as productive diversification for food, feed, fiber, and fuels. However, in developing countries, there is malnutrition by an inadequate diet caused by deficiency in quality or quantity of food. Therefore, options are needed for the production of foods, mainly of high protein content such as edible mushroom from by-products. In Veracruz, Mexico, there is a large megadiversity of wastes derived from endemic plants, fruits, legumes, pods, leaves, straws, and flowers that are generated in a large amount and are disposed off through open-field burning without a specific use. The objective was to evaluate the potential of 30 nonconventional by-products and wastes for the production of low-cost oyster mushrooms Pleurotus ostreatus. Biological efficiency (BE) varied from 17.65 to 180% and at least the 60% of the evaluated substrates (BE greater than 50%) are viable for the production of mushroom Pleurotus especially in view of its low contamination in trials and abundance and availability and diversity throughout the agricultural year as wastes. Besides, the spent substrates were converted into organic manure compost, vermicompost and bocashi to close the cycle for new food production.