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With the aim to recommend an integrated alternative for the combined treatment of olive mill wastewater (OMW) and cotton residues (CR), and the production of high value and environmentally friendly products, two compost piles were set up. The first pile (control, pile 1) consisted of ginned CR, whereas the second (pile 2) was made of CR with the addition of OMW. A series of physicochemical parameters and the culturable microbial diversity in both piles were assessed. Co-composting (pile 2) displayed higher temperatures during the whole process, a prolonged second thermophilic phase and temperature values higher than 40 °C even after the thermophilic stage. Comparing the physicochemical parameters of the pile 2 with those of the pile 1, it was deduced that pH in the former was more acidic during the onset of the process; the EC values were higher throughout the process, while the levels of ammonium and nitrate nitrogen, as well as the NH4+/NO3− ratios, were lower at most of the sampling dates. By evaluating the abovementioned results, it was estimated that the co-composting process headed sooner toward stability and maturity, Isolated microorganisms from both piles were identified as members of the genera Brevibacillus, Serratia, Klebsiella, and Aspergillus, whereas active thermotolerant diazotrophs were detected in both piles at the 2nd thermophilic phase emerging a promising prospect upon further evaluation for enhancing the end-product quality. Our findings indicate that co-composting is an interesting approach for the exploitation of large quantities of agro-industrial residues with a final product suitable for improving soil fertility and health.