The effect of agro-industrial wastes (coffee pulp, rice straw, corncobs, and their mixtures) on the biological efficiency, nutritional composition, and antioxidant activity of Pleurotus djamor was evaluated. The biological efficiency was in a range of 8.26–95.95%. Coffee pulp mixed with other residues increases the biological efficiency of the mushroom. The content of protein, crude fat, fiber, carbohydrates, total polyphenols and antioxidant activity DPPH and ABTS were in the range of 21.61–27.09%, 0.77–2.26%, 13.32–19.40%, 41.45–51.06%, 1.74–3.03 mgGAE / g, 0.051–0.091mMTE / g and 0.067–0.133 mMTE / g respectively. An order of abundance was observed for macro-elements of Ca> P > K> Mg> Na and for microelements of Zn> Fe> Cu in the mushroom, similar order to that presented in the formulations where they were cultivated. It was found that the combinations of substrates improve the nutritional parameters of the mushroom, while the mineral content of the fruiting bodies was influenced by the mineral content of the substrate where they grow. The use of these residues allows obtaining a product with great nutritional and nutraceutical value through a simple, low-cost, and sustainable biotechnological process. • Antioxidant activity in P. djamor cultivated in agro-industrial wastes.. • Nutritional composition of P. djamor in different mixtures. • Antioxidants and proteins increased when grown in coffee pulp and corncobs. • A nutritious and nutraceutical product was obtained at low cost. • Contribution to cleaner production of P. djamor in agro-industrial wastes.