Guillermo Santo (born 4 June 1982 in Lanús) is an Argentine association football player who most recently played defensive midfielder for F.C. Motagua.
Santo began his playing career in 1998 with Club Atlético Platense, he has also played for El Porvenir and Chacarita Juniors in Argentina. Between 2005 and 2008 he played in Venezuela for Trujillanos FC, Mineros de Guayana and Deportivo Anzoátegui.