Vale do Javari is home to 3,000 indigenous peoples of Brazil with varying sorts of contact, including the Matis, the Matses, the Kulina, the Mayoruna, and others. The uncontacted indigenous peoples are estimated to be more than 2,000 individuals belonging to at least 14 tribes like the Isolados do Rio Quixito, Isolados do Itaquai (Korubo), Isolados do Jandiatuba, Isolados do Alto Jutai, Isolados do Sao Jose, Isolados do Rio Branco, Isolados do Medio Javari and Isolados do Jaquirana-Amburus. These are believed to be living deep inside its reservation areas. The uncontacted tribes live in some 19 known villages identified by air. According to Fabricio Amorim from Fundação Nacional do Índio, the region contains "the greatest concentration of isolated groups in the Amazon and the world".
Vale do Javari is the setting of The Unconquered: In Search of the Amazon's Last Uncontacted Tribes (2011) by National Geographic writer Scott Wallace. It details a 76-day expedition in 2002 led by Sydney Possuelo to find the status of the "Arrow People", an uncontacted tribe.