Two new indole alkaloids, 6-(4-methoxyphenoxy)-4-methoxy-2-methyl-1H-indole (1) and 6-(3,5-dimethoxyphenoxy)-4-methoxy-2-methyl-1H-indole (2), along with four known ones (3–6), were isolated from the fermentation products of the cigar tobacco-derived endophytic fungus Aspergillus oryzae. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compounds 1 and 2 were evaluated for their antibacterial and antioxidant activities. The results showed that compounds 1 and 2 exhibited good anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity with IZD of 22.4 ± 2.4 and 24.6 ± 2.2 mm, respectively. © 2022, Springer Science+Business Media, LLC, part of Springer Nature.