A new series of pyrano[4,3-b]pyrane 4a–l bearing 1H-pyrazole has been synthesized by one pot base catalyzed cyclocondensation reaction of 1H-pyrazole-4-carbaldehyde 1a–l, malononitrile 2 and 4-hydroxy-6-methylpyrone 3. All the synthesized compounds were screened against six bacterial pathogens, namely B. subtilis, C. tetani, S. pneumoniae, S. typhi, V. cholerae, E. coli and antifungal activity against, two fungal pathogens, A. fumigatus and C. albicans using broth microdilution MIC method. Some of the compounds are found to be equipotent or more potent than that of commercial drugs, against most of employed strains.