Sugars are natural and environmentally benign substances, which can offer various hydroxyl groups. The understanding of details of the hydroxyl interactions in the hydrophilic groups of sugar-based surfactants, as well as the related properties, is still indistinct. Here, novel d-gluconic acetal surfactants with bicyclic and monocyclic structures in the head group were designed and synthesized. The obtained surfactant with a bicyclic architecture exhibited excellent foamability and a multistimulus-responsive behavior toward foam stabilization. In addition, the control of foamability from defoaming and foaming could be achieved by changing pH values or bubbling gas of CO2/N2. To explore the structural effects such as hydroxyl groups and rigidity of the head group on the properties of sugar-based surfactants, another kind of amphiphilic molecule with various OH- groups and a monocycle in the head group was designed for comparison. These two series of amphiphilic molecules both exhibited good surface activity. However, only the d-gluconic acetal surfactant with a bicyclic structure and a smaller number of OH- groups exhibited excellent foamability. Further studies showed that the foam behaviors were attributed to the conformation and arrangement of the surfactant molecule at the surface layer with the assistance of hydrogen bonds formed by hydroxyl groups and H2O molecules. In addition, the surfactant could provide an environmentally friendly foamer in many potential applications.