To explore new agents of quinolone derivatives with high antibacterial activity, 7-(4-alkoxyimino- 3-methyl-3-methylaminopiperidin-1-yl)quinolones were designed and synthesized, and their activity against gram-positive and gram-negative strains was tested in vitro.  Sixteen target compounds were obtained.  Their structures were established by ¹H NMR, HRMS and X-ray crystallographic analysis.  Compounds 14k and 14m−14o show good antibacterial activity against the tested five gram-positive strains and five gram-negative strains (MIC: 0.25−16 μg·mL⁻¹), of which the most active compound 14o is 8-fold more potent than levofloxacin against S. pneumoniae (MIC: 4 μg·mL⁻¹), and comparable to levofloxacin against S. aureus, S. epidermidis,   E. faecalis and E. coli (MIC: 0.25−1 μg·mL⁻¹), but generally less potent than gemifloxacin.