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In this study, inhibitory effects of crude silk produced by 5th larval instar of moth Plodia interpunctella, as well as ethanol, acetone, ethyl acetate, hexane and dichloromethane silk extracts were evaluated against 18 bacterial strains (ATCC strains/isolates) and 6 fungal ATCC strains in vitro. Among the tested extracts, the acetone silk extract had the highest activity against Gram-negative bacteria, while all the extracts showed moderate to high activity against Grampositive bacteria and fungi. The dilution of 1/2, 1/4 of stock samples showed higher microbial activity. The crude silk was not bioactive. This is the first report on antimicrobial activity of different extracts of silk of P. interpunctella larvae. These results open new avenues for future research in using this major storage insect pest in biomedical applications. © 2020, Indian Academy of Sciences.