Some new 7-alkoxyhesperetin derivatives, 7-methoxy-(c), 7-butoxy-(d), 7-octyloxy-(e), 7-decyloxy-(f), and 7-dodecyloxyhesperetin(g), were synthesized and confirmed by UV, IR, 1 H NMR, and MS spectra data. The series of the synthesized compounds has been screened for their antibacterial activity in vitro and evaluated their structure-activity relationships. Substitution of the H with alkyl groups at C-7-OH led to significant change of their antibacterial activity. The antibacterial activity of 7-alkoxyhesperetin derivatives increased with the elongating of the length of aliphatic chain, and the maximum activity was reached at twelve carbon atoms. Compound f showed the highest antibacterial activity among all the compounds.