The presence of pharmaceutical products has raised emerging biorisks in aquatic environments. Fungi have been considered in sustainable approaches for the degradation of pharmaceutical compounds from aquatic environments. Soft rot fungi of the Ascomycota phylum are the most widely distributed among fungi, but their ability to biodegrade pharmaceuticals has not been studied as much as that of white rot fungi of the Basidiomycota phylum. Herein, we evaluated the capacity of the soft rot fungus sp. B2B to degrade pharmaceuticals under treatment of woody and nonwoody lignocellulosic biomasses. Nonwoody rice straw induced laccase activity fivefold compared with that in YSM medium containing polysaccharide. But B2B preferentially degraded polysaccharide over lignin regions in woody sources, leading to high concentrations of sugar. Hence, intermediate products from saccharification may inhibit laccase activity and thereby halt the biodegradation of pharmaceutical compounds. These results provide fundamental insights into the unique characteristics of pharmaceutical degradation by soft rot fungus sp. in the presence of preferred substrates during delignification.