Nine new meroterpenes (1-9) and one new dioxolanone derivative (10), along with seven known compounds (11-17), were isolated from solid cultures of the endophytic fungus Guignardia sp., obtained from Euphorbia sieboldiana. Their structures were elucidated by analysis of UV, IR, 1D and 2D NMR, and HRESIMS data, and their absolute configurations were determined by a combination of single-crystal X-ray studies, modified Mosher methods, and Rh2(OCOCF3)4- and Mo2(OCOCH3)4-induced electronic circular dichroism experiments. All compounds were evaluated for their inhibitory effects alone and with fluconazole on the growth and biofilms of Candida albicans. At 6.3 μg/mL combined with 0.031 μg/mL of fluconazole, compounds 8 and 16 were found to have prominent inhibition on the growth of C. albicans with fractional inhibitory concentration index values of 0.23 and 0.19, respectively. Combined with fluconazole, both of them (40 μg/mL for 8 and 20 μg/mL for 16) could also inhibit C. albicans biofilms and reverse the tolerance of C. albicans biofilms to fluconazole.