With just 75,000 people living in 80,000km², Madre de Dios is the least populated, least developed area of Peru. Puerto Maldonado is the only sizeable town in the entire region, with a population of about 30,000. The rural population is settled in small mixed subsistence communities along the rivers and roads. Roads are very few; transport is mostly by river. Madre de Dios has often been described as one of the last great wildernesses on earth, with 90% of its original forest cover intact.

Madre de Dios is home to 18 different ethnic groups of Amazon Indians who currently number about 10,000. This is only a fraction of their numbers at the beginning of the 20th Century; since the start of the rubber boom in the 1890s, their populations have been decimated by disease, slavery and murder. They are currently struggling to secure their land and resource rights through the Federation for Native Communities of Madre de Dios (FENAMAD), which was founded in the early ‘80s. The ethnic group in the Tambopata region is the Ese'eja (of the Takana linguistic group). Non-indigenous rural communities have formed the Federation for small farmers of Madre de Dios (FADEMAD) and are also struggling to secure land rights and improve their livelihoods.

The forests of Madre de Dios are some of the most biodiverse in the world. Intensive biological research over the last 25 years in a 5.5 km² area surrounding Explorers’ Inn, a tourist lodge established on the Tambopata river in the 1970s, has identified more species of birds (587+), butterflies (1230+) and many invertebrate groups than for any other location of equivalent size on Earth. The IUCN and WWF have identified Madre de Dios as a World Centre for Plant Diversity. It was records such as these, and the resultant boom in ecotourism, that led the Peruvian government to pass a decree declaring Puerto Maldonado the "biodiversity capital of Peru".