To simultaneously enrich, separate, and determine five fluoroquinolone antibiotics (FQs) in marine crude drugs (MCDs), seawater and seafood, we conducted this study using vortex assisted dispersed liquid-liquid microextraction (DLLME), followed by capillary electrophoresis (CE)-UV. A single-variable optimization was employed to examine the factors influencing the separation effect of CE and the extraction efficiency of DLLME, including buffer solution, organic solvent, separation voltage, extractant, dispersant, and sample solution pH. Under the optimal conditions, the baseline separation of the five FQs was achieved within 6 min. The analytical performance of the method was assessed using six types of actual samples, including three MCDs of hippocampus, clam, and kelp, seawater, and two seafood of prawn and pomfret, demonstrating good linearity ranging from 0.1-5 or 0.01-5 mu g/mL. The limits of detection (LODs) and limits of quantification (LOQs) for the five FQs in MCDs were 0.002 2-0.029 2 and 0.006 6-0.097 3 mu g/mL, respectively. The LODs and LOQs in seawater and seafood were 0.000 9-0.026 2 and 0.002 9-0.087 4 mu g/mL, respectively. The matrix effects of this method were evaluated in the hippocampus, seawater, and prawn, and the results show that DLLME could effectively eliminate matrix interference. Satisfactory recovery rates were achieved in all the six tested actual samples. This developed DLLME-CE method was proven simple to operate, accurate and reliable, with high sensitivity, making it suitable for the analysis of multiple antibiotic residues in complex matrices.