Malaria remains one of the most important diseases in the world, being lethal to 610 thousand individuals annually. The widespread resistance of P. falciparum to antimalarials emphasizes the urgent need for new therapies, as treatment remains the primary strategy to control the disease. Although combinations of synthetic drugs are used in treatment, medicinal plants are often utilized in folk medicine as a complement and/or alternative to treat human malaria, especially in poor endemic areas. This systematic review evaluates the antiplasmodial and/or antimalarial activities, as well as the ethnopharmacological use of plant species by traditional communities from South America, through a search in the PubMed Central and Science Direct databases. Among 346 articles selected using the keywords “Malaria”, “Plants”, “Traditional”, “Knowledge”, “Antimalarial” and “Amazon”, 27 were considered eligible. Plant species with no activities were used to a new search on Google, PubMed, and Science Direct. Of the 389 species or genera from 88 botanical families evaluated, most studies were conducted in Peru, with leaves being the primary plant part used for treatment and/or prevention. Out of the analyzed species, excluding 30 mentioned only by genus, 185 had their extracts, fractions, or pure substances assessed, and only nine species had both in vitro and in vivo activity. Among the 174 species cited by traditional communities evaluated, with no data for activity, 66 presented results when a new literature search was performed. The Chayahuita ethnicity was the community providing more traditional knowledge about malaria treatment. Most plant species mentioned in the articles indicated for treatment and/or prevention of malaria have not yet been evaluated for antiplasmodial and antimalarial activities. Collecting ethnopharmacology information of plants is important, since their use for malaria treatment significantly increases the chances of finding a plant to be used as antimalarial substitutes.