Antibacterial piezoelectric materials have broad application prospects in the medical field because of their broad-spectrum antibacterial properties and no bacterial drug resistance. At present, one of the main problems in the application of piezoelectric materials is the low electrocatalytic efficiency, which limits its application in antibacterial field. In this study, a piezoelectric antibacterial (PLGA/Zn-KNN) scaffold was fabricated by incorporating zinc oxide (ZnO) into potassium-sodium niobate (KNN) and composited with a poly (lactic-co-glycolic acid) (PLGA) to achieve multicombination antibacterial for bone infection. The physicochemical properties of piezoelectric antibacterial scaffolds were analyzed. Bacterial, cell, and animal experiments were performed to characterize the antibacterial and infection treatment capabilities of piezoelectric scaffolds. The piezoelectric properties of the PLGA/Zn-KNN scaffold were enhanced by embedding ZnO particles into the KNN solid solution matrix. Furthermore, the piezoelectric scaffold released zinc ions, and electrical stimulation driven by ultrasound resulted in significant antibacterial effects through direct and immunoregulatory antibacterial pathways. Mechanistic investigation suggested that extracellular matrix ligands and complement and coagulation cascades may have a moderate effect on macrophage phagocytosis. This work highlights potential application methods for fabricating novel antibacterial hybrid piezoelectric scaffolds and engineering macrophages with immunoregulatory antibacterial activity.