This chapter explores how design can facilitate the transformation of hospitality-related systems of spaces, products and services into increasingly more sustainable models. By adopting a regenerative perspective to address the complexity of these systems, it is possible to outline processes that enhance biodiversity, mitigate the damage inflicted by human activity, and restore ecological balance, as the tourism sector exerts a considerable impact on natural ecosystems (U.N. Environmental Program, 2023). This approach aims not only at mitigating its effects, but rather to generate a net positive one, reinstating conditions that enable the harmonious coexistence of flora, fauna, and human communities. The initial section of this chapter introduces a research-driven approach that establishes a conceptual foundation for embedding design-focused strategies into the planning and evolution of hospitality spaces within the tourism industry. The second section focuses instead on the analysis of relevant case studies for designers and stakeholders: on the one hand, research projects developed during research and didactical activities at Politecnico di Milano. On the other hand, case studies actively implemented and operating at high levels will also be featured in order to observe the potential practical and applicative outcomes and feedback of regenerative design methodologies. The featured projects deal with a range of topics, from soundscape ecology to water clean-up, from multispecies coexistence to the creative reuse of waste, but are unified in the belief that progress in the tourism industry lies in introducing and enhancing design strategies that implement regenerative approaches in hospitality business opportunities.