Fundación Soros–Guatemala focuses on broadening the participation of marginalized groups in public life, improving local economic development, advancing public health, promoting justice and rule of law, and using education and the media to promote tolerance and facilitate dialogue between different sectors of society in Guatemala.

To increase the participation of marginalized groups, particularly Mayans, in Guatemalan political and economic life, the foundation works with local communities on issues such as land distribution, labor rights, forest conservation, and access to legal support. It has also worked to incorporate traditional indigenous justice systems into mainstream legal practices. In an effort to fight the clandestine security forces that operate with impunity in Guatemala and threaten to provoke renewed political violence, the foundation has worked to bring global attention to the issue, helping establish an investigatory commission approved by the Guatemalan government and the United Nations.

HIV prevention is another priority for the foundation, which has focused its efforts on educating young people about HIV risks, promoting respect for the human rights of those living with HIV, and influencing related public policy. As part of its efforts to promote accountability in governance and the financial sector, the foundation supports local independent media and has launched a transparency project that will monitor relationships among banks, regulatory agencies, and consumers.