Background: Microbubbles are widely used as highly effective contrast agents to improve the diagnostic capability of ultrasound imaging. Mounting evidence suggests that ultrasound coupled with microbubbles has promising therapeutic applications in cancer, cardiovascular, and neurological disorders by acting as gene or drug carriers. The aim of this study was to identify the scientific output and activity related to ultrasound microbubble through bibliometric approaches.Methods: The literature related to ultrasound microbubble published between 1998 and 2019 was identified and selected from the Science Citation Index Expanded of Web of Science Core Collection on February 21, 2021. The Scopus database was also searched to validate the results and provided as supplementary material. Quantitative variables including number of publications and citations, H-index, and journal citation reports were analyzed by using Microsoft Excel 2019 and GraphPad Prism 8.0 software. VOS viewer and CiteSpace V were used to perform coauthorship, citation, co-citation, and co-occurrence analysis for countries/regions, institutions, authors, and keywords.Results: A total of 6088 publications from the WoSCC were included. The United States has made the largest contribution in this field, with the majority of publications (2090, 34.3%), citations (90,741, 46.6%), the highest H-index (138), and close collaborations with China and Canada. The most contributive institution was the University of Toronto. Professors De Jong N and Dayton P A have made great achievements in this field. However, the research cooperation between institutions and authors was relatively weak. All the studies could be divided into four clusters: “ultrasound diagnosis study,” “microbubbles’ characteristics study,” “gene therapy study,” and “drug delivery study.” The average appearing years (AAY) of keywords in the cluster “drug delivery study” was more recent than other clusters. For promising hot spots, “doxorubicin” showed a relatively latest AAY of 2015.49, followed by “nanoparticles” and “breast cancer.”Conclusion: There has been an increasing amount of scientific output on ultrasound microbubble according to the global trends, and the United States is staying ahead in this field. Collaboration between research teams still needs to be strengthened. The focus gradually shifts from “ultrasound diagnosis study” to “drug delivery study.” It is recommended to pay attention to the latest hot spots, such as “doxorubicin,” “nanoparticles,” and “breast cancer.”