Azo dyes released by the textile industries cause severe damage to the environment and living organisms. The degradation of azo dyes is widely studied using enzymatic methods. Laccase is a copper-containing enzyme that degrades the azo dyes into less toxic compounds. In this work, the crude laccase enzyme produced by the alkaliphile Pseudomonas mendocina in the degradation of mixed azo dye showed 0.386 U/mL activity at pH 8.5. A combination of enzymatic and green synthesized nanoparticles was used in the degradation of mixed azo dye. Laccase used in the degradation of mixed azo dyes showed 58.4% in 72 h, while the photocatalytic degradation of mixed azo dyes showed 15.9%. The degradation of azo dyes using copper iodide nanoparticles resulted in 15.8% degradation. However, it was noticed that the combined method of degradation of azo dyes involving both crude laccase and CuI nanoparticles gave a degradation of 62.3% in 60 min. Interaction of laccase enzyme with azo dyes using in silico analysis predicted the binding energy with reactive red (−7.19 kcal/mol), reactive brown (−8.57 kcal/mol), and reactive black dyes (−9.17 kcal/mol) respectively. © 2021, The Author(s).