The administrative-territorial reform, which is being carried out in Ukraine, has updated the search for new ways of endogenous development of its regions. Now, the real decentralization of power is one of the main priorities of the initiated changes. This should increase the institutional and managerial capacity of local governments in both individual communities and regions. At the same time, achieving this goal will be difficult if we ignore the current trends of globalization and the impact of globalization factors on the endogenous development of regions. However, recent practices show that globalization factors can have not only stimulating but also limiting effects. These factors can also reduce the efficiency of regional development potential. The case of the spread of quarantine restrictions in many countries caused by the COVID-19 coronavirus pandemic can serve as an example. As a result, the government institutions of different states and their regional local governments face a number of serious challenges of socio-economic nature. The negative factors of globalization impact on the endogenous development of regions in modern conditions include: non-tariff restrictions generated by environmental, security or socio-psychological motives; opportunistic behavior of residents or businesses; corruption and the shadow economy; insufficient quality of human and social capital. It results in restrictions on the free movement of people, goods and capital under the pretext of protecting citizens from viral threats or from potentially harmful consumer goods. Another argument is the ban on using dishonestly acquired financial resources. As opposed, the main positive aspects of globalization’s impact on endogenous development of regions include: activation of interregional and cross-border cooperation, improvement of regional institutional and information infrastructure, local governments’ openness to cooperate with foreign investors and international donor organizations, cultural integration and implementation of democratic practices of public administration in regions, including instruments of participatory governance.