Two novel pyridino-cyathane diterpenoids, pyristriatins A and B (1 and 2), together with striatin C (3) were isolated from cultures of Cyathus cf. striatus, a basidiomycete that was found during a field trip in northern Thailand. The pyristriatins showed antimicrobial effects against Gram-positive bacteria and fungi. The isolation, structure elucidation, relative configuration, and biological and cytotoxic activity are described. Their structures were assigned by HRMS and NMR spectroscopy. We also describe the first 2D NMR assignment of striatin C. Pyristriatins A and B are the first cyathane natural products featuring a pyridine ring.