Background: Microbes are mostly transferred through the hands and the nosocomial infections are extremely common. To combat the harmful effects of microbial burden in health care facilities, hand sanitizers are recommended for hand disinfection. Objective: The goal of this research is to conduct a systematic review of studies on the effectiveness of natural hand sanitizers. Methods: Under the PRISMA criteria, a systematic search was carried out (Recommended Reporting Items for Systematic Reviews and Meta Analyses) three databases were used to conduct the search: PubMed, Google Scholar, and Science Direct. Published from 2002 to 2024. The Key words for the survey were ‘Natural hand sanitizers, Hand hygiene, Disinfectant, Antibacterial activity. Following the finding of relevant papers, a critical appraisal was carried out in order to select those that would be appropriate for the systematic review. The study's inclusion criteria were surveys, clinical studies, no sample size limits, and only English literature. Result: The keywords led to the discovery of 65 relevant publications, 14 of which were suitable for the systematic review. Hand sanitizers of several kinds were investigated. It's used to stop the spread of infection and sickness. Conclusion: In this systematic review, it was concluded that the efficacy and the broad spectrum of natural hand sanitizers were significantly efficient which is important to boost the formulation's effectiveness as well as safety.