Abstract Background UNESCO biosphere reserves have historically hoped to play a crucial role in contributing to sustainable development by bringing about win-win outcomes for both biodiversity and socio-economic development. However, recent studies show of the need for a more thorough understanding of the interaction between conservation and socio-economics. Moreover, the nexus between conservation intervention and human development has been facing sizeable challenges due to the conflicting interests induced by rapid social and environmental challenges, such as climate change. This, therefore, raises the need for a deeper understanding of the relationship between natural conservation and socio-economic development. In this systematic review, we will enrich the understanding on the relationship between natural conservation and socio-economic development through examining the impacts of UNESCO biosphere reserves on socio-economic well-being in South East Asia countries. Method This systematic review stems from a systematic map by Eales et al (2020) to examine the impact of marine management and conservation interventions on human well-being in South East Asia. The systematic map documents multiple types of intervention and outcome and provides an overview on the topic. Building from the systematic map, this systematic review will be more focused on the intervention of UNESCO biosphere reserves and socio-economic outcomes, and will cover both terrestrial and marine UNESCO reserves. We will include any relevant studies identified by the systematic map. We will also conduct further searches in the English language and any other languages within the capability of the review team to include both academic papers and grey literature. Study screening will be conducted in two steps: title and abstract, and full-text. Selected studies (decisions based on pre-defined inclusion criteria) will be assessed for validity based on critical appraisal checklists. We will extract relevant information such as study site/area/year of designation, population, intervention, study design, type of study, outcome measurements and factors affecting the outcomes. A narrative synthesis will be conducted to investigate which aspects of socio-economic wellbeing have been affected by UNESCO biosphere reserves. We will undertake a quantitative synthesis if the available data is suitable. Keywords UNESCO biosphere reserves, conservation, Southeast Asia, human well-being, socio-economics