 Santa Isabel belongs to the Guarulhos macro region, thus it is part of the Greater São Paulo region as well.The municipality lies in the basins of the Rio Jaguari and the Rio Paraíba do Sul and 84% of the municipality is protected by environmental laws because of its significance as a potable water source 
The municipality contains part of the Mananciais do Rio Paraíba do Sul Environmental Protection Area, created in 1982 to protect the sources of the Paraíba do Sul.The area suffered ecologically from unauthorized uses and in 1996 the Ibirapitanga Reserve on the Rio dos Pilões was created to preserve one of the last stands of Brazilian Atlantic forest and to permit managed urban growth.