Hericium caput-medusae is an edible and medicinal mushroom closely relative to H. erinaceus. According to our detailed chemical investigation, two novel isoindolinone-containing meroterpene dimers, caputmedusins A (1) and B (2), as well as nine analogues, caputmedusins C–K (3–11), were isolated from the fermentation broth of H. caput-medusae. Their structures were elucidated by analyses of 1D and 2D NMR spectroscopic methods. The absolute configurations of 1–4 were speculated based on the specific optical rotation and biogenetic consideration. The absolute configurations of 10 and 11 were rationalized by the calculation of 1H NMR chemical shifts. Caputmedusins A–C (1–3) showed moderate inhibitory activity against α-glucosidase with the IC50 values of 39.2, 36.2 and 40.8μM, respectively.