This meta-analysis and systematic review examined the effects of psychedelic substances on death anxiety, specifically evaluating whether psychedelic experiences are associated with statistically significant reductions in death anxiety. A systematic search identified 8 studies suitable for meta-analysis and 10 additional studies for systematic review. Using a random-effects model, the meta-analysis revealed a significant overall effect (Cohen's = 0.70; 95% confidence interval [0.42, 0.97]), indicating a moderate-to-large reduction in death anxiety following psychedelic administration. Subgroup analyses showed stronger effects in clinically controlled settings compared to the general population. A mixed-effects meta-regression also indicated that particularly mystical experiences were positively associated with reductions in death anxiety ( = 4.90, = 0.050). Moderator effects by substance type were not significant. The qualitative review reaffirmed these results and identified themes of ego dissolution, emotional catharsis, and living in the present moment. Psychedelic-assisted interventions may be effective for reducing death anxiety, particularly in end-of-life care. However, limitations include a small number of studies, potential publication bias, and high heterogeneity in outcome measurement. Future research should employ more methodologically rigorous trials in order to clarify the mechanisms of psychedelic-assisted approaches to death anxiety. d B p