The health benefits of urban green space are widely discussed in the literature, however, there is limited evidence and field experiments on how street-level green interventions affect mental health and well-being (MHWB) outcomes. Such experiments are notoriously difficult due to the complex nature of urban environments, which makes it challenging to identify and match control sites to intervention sites with precision. This paper addresses this challenge by outlining a methodological framework for such matching and tests its validity by piloting the NeuroDesign Index Urban (NDIX-Urban) in two real-life before-and-after street redevelopment projects in North London. The framework draws on health and streetscape research that identifies key neighbourhood- and street-level characteristics influencing MHWB in urban contexts. These characteristics underpin a multi-level, spatially layered approach. First, neighbourhoods are filtered using QGIS-based analysis of socio-economic status, crime and safety levels, land use, and green coverage. Second, environmental audits and site visits are conducted at street level to identify similar control sites in terms of traffic flow, pedestrian activity, and the type and quality of buildings. The matching of control and intervention sites is validated using the NDIX-Urban survey, administered to 122 participants. Data from the four sites was analysed to assess the framework’s effectiveness in selecting highly comparable control sites, based on NDIX-Urban categories, including safety and accessibility, sensory, emotional, cognitive, social, and naturalness. The paper concludes that the control site selection procedure developed within the framework is robust, providing a spatial and structured methodology for future urban field experiments.