With the global bio-based leather market projected to reach $902.4 million by 2028 at a CAGR of 6.2% from 2023 to 2028, the fashion and textile industry—recognised as the third-largest global polluter—faces mounting pressure to adopt more sustainable practices. Widespread reliance on synthetic materials has contributed to escalating chemical waste and microplastic pollution, highlighting the urgent need for eco-friendly alternatives. In response, there is growing interest in bio-based materials—derived from renewable sources—that promise both renewability and biodegradability. Next-generation innovations, such as bacterial cellulose and mycelium-based “leather,” have thus emerged as compelling contenders to replace conventional textiles. This chapter offers a comprehensive exploration of leather alternatives, examining their design, production processes, and broader environmental implications. It begins with an in-depth analysis of traditional leather, comparing genuine animal leather with synthetic polyurethane leather. Their respective production processes, ecological footprints, and ethical considerations are critically assessed, laying the groundwork for a discussion on emergent bio-based approaches. Subsequently, the latest advancements in bacterial cellulose and mycelium-based “leather” are introduced, emphasising their potential to mitigate the environmental and ethical concerns associated with conventional materials. Additionally, the chapter presents a comparative analysis of the economic value and environmental impacts of these varied leather alternatives. Sustainability metrics and lifecycle assessments are explored to assess the feasibility and long-term promise of bio-based leather. The chapter concludes by situating these innovations within the broader sustainable fashion landscape, underscoring the vital role of bio-innovation and charting future trends that could reshape the global leather and fashion sectors.