The aim of the current study was to detect various secondary metabolites in the extract of Debregeasia salicifolia, and to synthesize stable silver/gold nanoparticles (Ag/AuNPs) from D. salicifolia methanol crude extract. The antioxidant, antibacterial, and antifungal activities of the methanol crude extract, various isolated fractions, and the synthesized nanoparticles were evaluated. Phytochemical analyses of the methanol extract/fractions indicated the presence of tannins, saponins, flavonoids, steroids, terpenoids, coumarins, emodins, and soluble starch. Gold and silver nanoparticles have been subsequently synthesized from the methanol crude extract by green synthesis, and characterized by UV and IR spectroscopic techniques. Size of the particles was determined with the aid of an atomic force microscope (AFM). The results revealed that the size of AuNPs was 5-100 nm, and that of AgNPs was in the range 5-100 nm. Bioactivity screening revealed that chloroform and n-hexane fractions exhibited significant 2,2-diphenyl-1-picrylhydrazyl (DPPH·) radical scavenging potential against quercetin. Additionally, the extract/fractions and AuNPs were also subjected to antimicrobial activity screening against a number of strains of microbes. Among extracts, n-hexane fraction showed good antifungal activity as compared to other fractions, whereas in the case of anti-bacterial activity, extract and fractions were active against Gram positive and Gram negative bacterial strain. AuNPs were exhibited moderate activity against all tested bacterial strains.