Electric stimulation has been used in changing the morphology, status, membrane permeability, and life cycle of cells to treat certain diseases such as trauma, degenerative disease, tumor, and infection. To minimize the side effects of invasive electric stimulation, recent studies attempt to apply ultrasound to control the piezoelectric effect of nano piezoelectric material. This method not only generates an electric field but also utilizes the benefits of ultrasound such as non-invasive and mechanical effects. In this review, important elements in the system, piezoelectricity nanomaterial and ultrasound, are first analyzed. Then, we summarize recent studies categorized into five kinds, nervous system diseases treatment, musculoskeletal tissues treatment, cancer treatment, anti-bacteria therapy, and others, to prove two main mechanics under activated piezoelectricity: one is biological change on a cellular level, the other is a piezo-chemical reaction. However, there are still technical problems to be solved and regulation processes to be completed before widespread use. The core problems include how to accurately measure piezoelectricity properties, how to concisely control electricity release through complex energy transfer processes, and a deeper understanding of related bioeffects. If these problems are conquered in the future, piezoelectric nanomaterials activated by ultrasound will provide a new pathway and realize application in disease treatment.