Cotton-based textile industries sustain millions of people’s livelihoods in India and globally. During cotton processing, a huge amount of cotton wastes and byproducts are generated and are usually landfilled or incinerated. Consequently, textile industries are facing difficulties in solid-waste management, which is the cause of environmental pollution and health hazards. Cotton wastes, mainly comprised of cellulose, hemicellulose, and lignin, represent a sustainable feedstock for the fermentative production of value-added bioproducts using microorganisms. Advances in microbial biotechnology are aiding in facilitating the effective valorization of cotton waste into valuable products. Cotton waste has been utilized for microbial production of biomethane and biohydrogen. The potential of modern metabolic engineering tools such as PCR-based DNA sequencing and assembly, genome editing, CRISPR, and cell surface engineering could develop microbial strain with enhanced hydrogen and methane yield. This book chapter highlights the aspects of cotton waste/byproducts, their structural composition, pretreatment strategies, and microbial approaches for their bioconversion into biomethane and biohydrogen. This chapter presents an innovative pathway for the cotton processing industry to achieve a waste-to-wealth solution through microbial-based biorefineries.