A simple, highly efficient, and green method is developed for the synthesis of pyrano [2,3-d] pyrimidine derivatives via Knoevenagel and Michael addition in the presence of nano CuO-Ag as a catalyst. The structures of synthesized target compounds 5a-l were confirmed by spectral and elemental analysis and were screened for their antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH), H 2 O 2 , and NO methods. Their antibacterial activity against Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli, against Gram-positive bacteria such as Bacillus subtilis and Staphylococcus aureus, and antifungal activity against Candida albicans and Candida glabrata was also evaluated. The compounds showed higher bacterial activity than the standard used. Compounds 5b, 5d, 5g, 5h, and 5i exhibited higher free radical scavenging activity than the standard butylated hydroxy toluene (BHT). Compounds 5b, 5d, and 5h showed higher activity on Gram-positive bacteria, and compounds 5b, 5d, 5h, and 5i showed higher activity on Gram-negative bacteria than that of standard tetracycline. Compounds 5b, 5j, and 5l showed much higher antifungal activity against Candida globrata and C. albicans than that of standard Griseofulvin. K E Y W O R D S antibacterial, antifungal, antioxidant, nano CuO-Ag, pyrano [2,3-d] pyrimidines