BackgroundRespondent-driven sampling (RDS) is a nonprobability sampling technique that allows the extrapolation of its outcome to the target population. This approach is typically used to overcome the difficulties in studying hidden or difficult-to-reach groups.ObjectiveThe purpose of this protocol is to generate a systematic review on the accumulation of biological and behavioral data of female sex workers (FSWs) through different surveys that use the RDS method from around the world in the near future. The future systematic review will discuss the initiation, actualization, and problems of RDS during the accumulation of biological and behavioral data of FSWs through surveys from around the world.MethodsThe behavior and biological data of FSWs will be extracted from peer-reviewed studies published between 2010 and 2022 and that are acquired through RDS. Using PubMed, Google Scholar, the Cochrane database, Scopus, Science Direct, and the Global Health network, all papers that are available will be obtained using the search phrases “respondent-driven” and “Female Sex Workers” OR “FSW” OR “sex workers” OR “SW.” According to STROBE-RDS (Strengthening the Reporting of Observational Studies in Epidemiology for Respondent-Driven Sampling) criteria, the data will be retrieved through a data extraction form and will be organized using World Health Organization classifications of areas. The Newcastle-Ottawa Quality Assessment Scale will be used to measure bias risk and overall study quality.ResultsThe future systematic review that will be generated from this protocol will offer evidence for or against the claim that using the RDS technique to recruit participants from “hidden” or “hard-to-reach” populations is the best strategy. The results will be disseminated through a peer-reviewed publication. Data collection started on April 1, 2023, and the systematic review is expected to be published by December 15, 2023.ConclusionsA minimum set of parameters for specific methodological, analytical, and testing procedures, including RDS methods to evaluate the overall quality of any RDS survey, will be provided by the future systematic review, in accordance with this protocol, to assist researchers, policy makers, and service providers in improving RDS methods for the surveillance of any key population.Trial RegistrationPROSPERO CRD42022346470; https://tinyurl.com/54xe2s3kInternational Registered Report Identifier (IRRID)DERR1-10.2196/43722