The dichloromethane extract of Talaromyces convolutus cultivated on barley exhibited antifungal activity against Candida albicans. In the course of a search for the active compounds, four new tetramic acid derivatives, talaroconvolutins A (1), B (2), C (3), and D (4), were isolated along with ZG-1494alpha (5), and mitorubrin derivatives. The structures of talaroconvolutins A-D (1-4) were established on the basis of spectroscopic and chemical investigations and chemical correlations. The antifungal activity of the talaroconvolutins against the pathogenic fungi Aspergillus fumigates, Aspergillus niger, C. albicans, and Cryptococcus neoformans was determined.