Five new chromone methide polymers, (±)-amplisins A–D (1–4) and amplisin E (5), were isolated from a new fungicolous fungus Amplistroma fungicola. Compounds 1–5 were determined to have unusual chemical skeletons with two or three chromone methide groups linked with different polyketides. A non-enzymatic 1,4-Michael addition of chromone methide was verified in the biosynthesis of 1–5. Compounds 1 and 2 showed inhibition of PTP1B and stimulation of glucose uptake in insulin-resistant HepG2 cells. Compounds 3–5 exhibited strong NO inhibition of LPS-activated macrophages.