<p>Syphilis remains a persistent global health concern despite the availability of effective treatment. Regular screening is essential for prevention and early detection, yet clinic-based testing uptake is often limited by stigma, accessibility, and lengthy procedures. Home-based syphilis self-testing has emerged as an alternative approach to expand syphilis testing access. This scoping review synthesized current evidence on acceptability, barriers, and facilitators of home-based syphilis self-testing and identified gaps in existing literature. A systematic search of peer-reviewed studies published between January 2001 and March 2025 was conducted in PubMed, CINAHL, Embase, and Scopus. This review followed PRISMA-ScR and Arksey and O’Malley’s scoping review framework. Data were analyzed thematically guided by the socio-ecological model. Eight studies met the inclusion criteria. Home-based syphilis self-testing was generally acceptable across populations and settings. Most barriers and facilitators were identified at the individual level. The primary barrier that emerged was the difficulty of blood sampling through finger prick, followed by low risk perception, limited knowledge, and concerns about accuracy. Facilitators included enhanced privacy, convenience, and rapid results; prior testing experience also facilitated using a home-based syphilis self-test. Partners, healthcare providers, and community context, acted as both facilitators and barriers, influencing the individual's willingness to test. Home-based syphilis self-testing has the potential to increase syphilis testing uptake and early detection. To fully understand its potential, further research and strategies are needed to support independent testing and supportive environments, and to adopt home-based syphilis self-testing in real-world settings.</p>