HIV-related stigma is a major barrier to HIV testing and care engagement. Despite efforts to use mass media to address HIV-related stigma, their impact on reducing HIV-related stigma remains unclear. Thus, we conducted a systematic review and meta-analysis of peer-reviewed publications quantitatively examining the impact of mass media exposure on HIV-related stigma reduction and published from January 1990 to December 2020. Of 388 articles found in the initial screening from scientific databases, 19 met the inclusion criteria and were included in the systematic review. Sixteen articles reported the quantitative effect of mass media exposure on HIV-related stigma and were included in the meta-analysis. Systematic review results showed considerable heterogeneity in studied populations with a few interventions and longitudinal studies. Results suggested a higher interest in utilizing mass media by health policymakers in developing countries with greater HIV prevalence to reduce HIV-related stigma. Meta-analysis results showed a modest impact of mass media use on HIV-related stigma reduction. Despite heterogeneity in the impact of mass media on HIV-related stigma, Egger's regression test and funnel graph indicated no evidence for publication bias. Results demonstrated an increase in the impact of mass media on reducing HIV-related stigma over time and no correlation between the HIV prevalence in countries and the impact of mass media. In summary, mass media exposure has a modest and context-specific impact on HIV-related stigma reduction. More large-scale mass media interventions and studies addressing the impact of mass media on different forms of stigma are required to inform policies.