Treponema pallidum, a common pathogen in sexually transmitted diseases, has emerged as a significant public health threat in recent decades, showing a gradual increase in global prevalence. Antibiotics have been the primary method to treat Treponema pallidum infections. However, high-dose antibiotic use in clinical trials has raised concerns and unveiled a series of issues. This paper employs a literature review approach to summarize and compare scientific studies conducted in various countries and regions regarding Treponema pallidum in recent years. It aims to introduce and summarize the drug resistance of Treponema pallidum and the current progress in treatment. Studies indicate widespread resistance of Treponema pallidum to macrolides, while no resistance has been found to first-line drugs like benzathine penicillin and other alternative medications. Presently, benzathine penicillin remains pivotal in syphilis treatment. Alternatives such as ceftriaxone, second-generation tetracyclines, amoxicillin, and adjunctive immunomodulators, after clinical trials, have been used in early or late-stage syphilis treatment and prevention. The concept and research direction of syphilis vaccines are emerging and are poised to be a crucial approach in curtailing Treponema pallidum transmission. Diversified drug treatment strategies and the development of syphilis vaccines hold significant implications in safeguarding public health and ensuring global health security.