Biofilm formation by most pathogenic bacteria is considered as one of the key mechanisms associated with virulence and antibiotic resistance. Biofilm-forming bacteria adhere to the surfaces of biological or implant medical devices and create communities within their self-produced extracellular matrix that are difficult to treat by existing antibiotics. There is an urgent need to synthesize and screen structurally diverse molecules for their antibiofilm activity that can remove or minimize the bacterial biofilm. The development of carbohydrate-based small molecules as antibiofilm agents holds a great promise in addressing the problem of the eradication of biofilm-related infections. Owing to their structural diversity and specificity, the sugar scaffolds are valuable entities for developing antibiofilm agents. In this perspective, we discuss the literature pertaining to carbohydrate-based natural antibiofilm agents and provide an overview of the design, activity, and mode of action of potent synthetic carbohydrate-based molecules.