While removal of antibiotics in constructed wetland treatment systems (CWTS) has been described previously, few studies examined the synergistic effect of multiple design and operational parameters for improving antibiotic removal. This review describes the removal of 35 widely used antibiotics in CWTS covering the most common design parameters (flow configuration, substrate, plants) and operational parameters (hydraulic retention time/hydraulic loading rates, feeding mode, aeration, influent quality), and discusses how to tailor those parameters for improving antibiotic removal based on complex removal mechanisms. To achieve an overall efficient removal of antibiotics in CWTS, our principal component analysis indicated that optimization of flow configuration, selection of plant species, and compensation for low microbial activity at low temperature is the priority strategy. For instance, a hybrid-CWTS that integrates the advantages of horizontal and vertical subsurface flow CWTS may provide a sufficient removal performance at reasonable cost and footprint. To target removal of specific antibiotics, future research should focus on elucidating key mechanisms for their removal to guide optimization of the design and operational parameters. More efficient experimental designs (e.g., the Box–Behnken design) are recommended to determine the settings of the key parameters. These improvements would promote development of this environmentally friendly and cost-efficient technology for antibiotic removal.