Muchimangins are benzophenone-xanthone hybrid polyketides produced by Securidaca longepedunculata. However, their biological activities have not been fully investigated, since they are minor constituents in this plant. To evaluate the possibility of muchimangins as antibacterial agent candidates, five muchimangin analogs were synthesized from 2,4,5-trimethoxydiphenyl methanol and the corresponding xanthones, by utilizing p-toluenesulfonic acid monohydrate for the Brønsted acid-catalysis. The antibacterial assays against Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and Gram-negative bacteria, Klebsiella pneumoniae and Escherichia coli, revealed that the muchimangin analogs (±)-1,3,6,8-tetrahydroxy-4-(phenyl-(2',4',5'-trimethoxyphenyl)methyl)-xanthone (1), (±)-1,3,6-trihydroxy-4-(phenyl-(2',4',5'-trimethoxyphenyl)methyl)-xanthone (2), and (±)-1,3-dihydroxy-4-(phenyl-(2',4',5'-trimethoxyphenyl)methyl)-xanthone (3) showed significant activities against S. aureus, with MIC values of 10.0, 10.0, and 25.0μM, respectively. Analogs (±)-1 and (±)-2 also exhibited antibacterial activities against B. subtilis, with MIC values of 50.0 and 12.5μM, respectively. Furthermore, (+)-3 enhanced the antibacterial activity against S. aureus, with a MIC value of 10μM.