Abstract: A chemical investigation on the fermentation products of Sanghuangporus sanghuang led to the isolation and identification of fourteen secondary metabolites ( 1 − 14 ) including eight sesquiterpenoids ( 1 − 8 ) and six polyphenols ( 9 − 14 ). Compounds 1 − 3 were sesquiterpenes with new structures which were elucidated based on NMR spectroscopy, high resolution mass spectrometry (HRMS) and electronic circular dichroism (ECD) data. All the isolates were tested for their stimulation effects on glucose uptake in insulin-resistant HepG2 cells, and cellular antioxidant activity. Compounds 9 − 12 were subjected to molecular docking experiment to primarily evaluate their anti-coronavirus (SARS-CoV-2) activity. As a result, compounds 9 − 12 were found to increase the glucose uptake of insulin-resistant HepG2 cells by 18.1%, 62.7%, 33.7% and 21.4% at the dose of 50 μmol·L⁻¹, respectively. Compounds 9 − 12 also showed good cellular antioxidant activities with CAA₅₀ values of 12.23, 23.11, 5.31 and 16.04 μmol·L⁻¹, respectively. Molecular docking between COVID-19 M^pro and compounds 9 − 12 indicated potential SARS-CoV-2 inhibitory activity of these four compounds. This work provides new insights for the potential role of the medicinal mushroom S. sanghuang as drugs and functional foods.