BackgroundPrecarious employment is a significant determinant of population health and health inequities and has complex public health consequences both for a given nation and internationally. Precarious employment is conceptualized as a multi-dimensional construct including but not limited to employment insecurity, income inadequacy, and lack of rights and protection in the employment relation, which could affect both informal and formal workers. The purpose of this review is to identify, appraise, and synthesize existing research on the effectiveness of initiatives aiming to or having the potential to eliminate, reduce, or mitigate workers’ exposure to precarious employment conditions and its effects on the health and well-being of workers and their families.MethodsThe electronic databases searched (from January 2000 onwards) are Scopus, Web of Science Core Collection, and PubMed, along with three institutional databases as sources of grey literature. We will include any study (e.g. quantitative, qualitative, or mixed-methods design) evaluating the effects of initiatives that aim to or have the potential to address workers’ exposure to precarious employment or its effects on the health and well-being of workers and their families, whether or not such initiatives were designed specifically to address precarious employment. The primary outcomes will be changes in (i) the prevalence of precarious employment and workers’ exposure to precarious employment and (ii) the health and well-being of precariously employed workers and their families. No secondary outcomes will be included. Given the large body of evidence screened, the initial screening of each study will be done by one reviewer, after implementing several strategies to ensure decision-making consistency across reviewers. The screening of full-text articles, data extraction, and critical appraisal will be done independently by two reviewers. Potential conflicts will be resolved through discussion. Established checklists will be used to assess a study’s methodological quality or bias. A narrative synthesis will be employed to describe and summarize the included studies’ characteristics and findings and to explore relationships both within and between the included studies.DiscussionWe expect that this review’s findings will provide stakeholders interested in tackling precarious employment and its harmful health effects with evidence on effectiveness of solutions that have been implemented to inform considerations for adaptation of these to their unique contexts. In addition, the review will increase our understanding of existing research gaps and enable us to make recommendations to address them. Our work aligns with the sustainable development agenda to protect workers, promote decent work and economic growth, eliminate poverty, and reduce inequalities.Systematic review registrationPROSPERO CRD42020187544.