Objectives: Constant exposure to trauma and death adversely affects the physical, emotional, and mental stability of the helping professionals, leading to compassion fatigue (CF). Although research has explored the effect of various psychological interventions (PIs) on CF, no studies have quantitatively synthesized their effectiveness. Thus, the current systematic review and meta-analysis address this gap by examining the efficacy of PIs in reducing CF among helping professionals. Methods: Databases such as Scopus, Web of Science, PubMed, JSTOR, ScienceDirect, and Google Scholar were searched to identify studies published between 2004 and 2023. Quantitative studies published in English that used any PI to reduce CF of helping professionals were selected for analysis. The risk of bias in studies was evaluated using Joanna Briggs Institute (JBI) checklists and the National Heart, Lung, and Blood Institute quality assessment tool. Results: Of the 1995 records identified from databases, 82 intervention studies were included in the systematic review, and 11 randomized controlled trials were chosen for meta-analysis. Post-intervention means and SDs of the intervention group and the control group were used to run the meta-analysis. Random effects meta-analysis results revealed that PIs are highly effective in reducing CF (standardized mean difference (SMD)=?0.95; 95% CI, ?1.63 to ?0.27; P=.006). Conclusion: Evidence suggests that PIs, especially online-delivered PIs, could reduce the CF of helping professionals. Health policymakers, concerned authorities, and intervention designers should focus on reducing the CF of helping professionals, as they need to work with vulnerable populations efficiently.