Fourteen previously undescribed sesterterpenoids (1− 14) were isolated from Bipolaris maydis. Their structures with absolute configurations were elucidated by NMR, HRESIMS, DP4+ calculations, ECD calculations, single-crystal X-ray diffraction analyses, and the modified Mosher's method. Compounds 1−5 possess an uncommon 5/ 11 bicyclic ring system identified from B. maydis for the first time. Compounds 6−14 have a 5/8/5 tricyclic ring system, and these compounds both possess carbonyl groups in ring A. Compound 10 showed significant reversal of paclitaxel resistance in cancer cells.