On-street parking is a commonly used form of parking facility as part of transportation infrastructure. However, the emergence of connected and autonomous vehicles (CAVs) is expected to significantly impact parking in the future. This study aims to investigate the impacts of on-street parking regulations for CAVs on the environment, safety and mobility in mixed traffic fleets. To achieve this goal, a calibrated and validated network model of the city of Leicester, UK, was selected to test the implementation of CAVs under various deployment scenarios. The results revealed that replacing on-street parking with driving lanes, cycle lanes, and public spaces can lead to better traffic performance. Specifically, there could be a 27–30% reduction in travel time, a 43–47% reduction in delays, more than 90% in emission reduction, and a 94% reduction in traffic crashes compared to the other tested measures. Conversely, replacing on-street parking with pick-up/drop-off stations may have a less significant impact due to increased stop-and-go events when vehicles pick-up and drop-off passengers, resulting in more interruptions in the flow and increased delays. The paper provides examples of interventions that can be implemented for on-street parking during a CCAM era, along with their expected impacts in order for regional decision-makers and local authorities to draw relative policies. By replacing on-street parking with more efficient traffic measures, cities can significantly improve mobility, reduce emissions, and enhance safety.