The transport sector in the selected Greater Mekong Sub-region (GMS) countries namely, Cambodia, Lao PDR, Thailand, and Vietnam was one of the large carbon dioxide (CO2) emission sources in 2015 of which, the road transport contributed the largest CO2 emissions in the transport sector. The transport sector of these countries emitted 23.3% of the total CO2 emissions in 2015. The potential of Greenhouse Gas (GHG) mitigation in the road transport is huge as vehicle technologies keep advancing. Therefore, this study presents mitigating GHG emissions from the road transport of the selected GMS countries using scenario-based analysis. Besides the Business-as-Usual (BAU) scenario, three mitigation scenarios: Alternative Fuel (AF), Modal Shift (MS), and Electric Vehicle (EV) were developed. In addition, each countermeasure scenario is divided into two levels namely, low-ambition and high-ambition levels of GHG mitigation. The Low Emissions Analysis Platform (LEAP) model is used to estimate the energy demand and GHG emissions. The findings of the study show that the total GHG emissions in the road transport of the selected GMS countries in 2050 will be reduced by 69.75% in the high EV (EVH) scenario, 26.15% in the high AF (AFH) scenario, and 52.24% in the high MS (MSH) scenario. Results reveal that EVs have a high potential to mitigate GHG emissions in the road transport. Therefore, policymakers should encourage people to shift from conventional vehicles to EVs. In addition, the government should strive to attract EV manufacturers and provide incentives to those firms as well as EV owners. Furthermore, the electricity supply for EVs should come from green energy.