Fungi have a unique metabolic plasticity allowing them to produce a wide range of natural products. Since the discovery of penicillin, an antibiotic of fungal origin, substantial efforts have been devoted globally to search for fungal-derived natural bioactive products. Andean region forests represent one of the few undisturbed ecosystems in the world with little human intervention. While these forests display a rich biological diversity, mycological and chemical studies in these environments have been scarce. This review aims to summarise all the efforts regarding the chemical or bioactivity analyses of Agaricomycetes (Basidiomycota) from southern South America environments. Overall, herein we report a total of 147 fungal species, 21 of them showing chemical characterisation and/or biological activity. In terms of chemical cores, furans, chlorinated phenol derivatives, polyenes, lactones, terpenes and himanimides have been reported. These natural products displayed a range of biological activities including antioxidant, antimicrobial, antifungal, neuroprotective and osteoclast-forming suppressing effects.