Liquid crystalline molecularly imprinted polymers (LC-MIPs) were low cross-linking MIPs (5–20 mol%) by introducing a LC monomer into the MIP polymerization system to keep the shape of the imprinted cavities due to additional interactions between the mesogenic groups. The multiwalled carbon nanotubes (MWCNTs) coated LC-MIP (MWCNT@LC-MIP) was the first fabricated as a novel floating interaction-controlled DDS. The synthesis was achieved by adding 9-vinylanthracene to obtain the high-density vinyl group functionalized MWCNTs firstly, and then polymerization of LC MIPs was performed on the surface of MWCNTs using a mixture of methacrylic acid, ethylene glycol dimethacrylate, and 4-methyl phenyl dicyclohexyl ethylene (LC monomer) with levofloxacin (LVF) as model template drug. Both template/functional monomer ratio and levels of crosslinker were optimized to obtain the best imprinting factor. Characterizations of polymer were investigated by the transmission electron microscope, nitrogen adsorption, thermogravimetric analysis, Fourier transform infrared spectra and floating behavior studies. The imprinting effect was confirmed by the adsorption isotherms, adsorption kinetics and effect of selectivity. In vitro release studies were examined by the LVF-loaded MWCNT@LC-MIP and the control samples, MWCNT@LC-NIP, MWCNT@MIP, MWCNT@NIP and the bare MWCNT using acetonitrile as the dissolute medium. The release profiles showed an obvious zero-order release of LVF from MWCNT@LC-MIP, which exhibited 3.8 μg/h of the release rate with duration of about 20 h. In vivo pharmacokinetic study displayed the relative bioavailability of the gastro-floating MWCNT@LC-MIP was 578.9%, whereas only 58.0% of MWCNT@MIP and 11.7% of the bared MWCNT. As a conclusion, MWCNT@LC-MIP showed potentials for oral administration by the innovative combination of floating and controlled release properties.