Abstract The objective of this systematic review and meta-analysis was to investigate whether the administration of branched-chain amino acids (BCAAs) reduces exercise-induced muscle damage (EIMD) markers following eccentric exercise (EE) compared to a placebo (PL). The Cochrane bias risk tool and NutriGrade scale were used to critically evaluate the included studies. Forest plots were used to visualize the standardized mean differences (SMD) and p-values. The included studies were randomized controlled trials with either a placebo or crossover randomized design. The assessment of EIMD markers was compared between the intervention (BCAA) and placebo situations at 0, 24, 48, 72, and 96 hours after the EE protocol. Subgroup analyses were conducted to assess the effects of BCAA intake on creatine kinase concentration based on follow-up times (immediately, 24 hours, 48 hours, 72 hours, 96 hours), dosage (≥ 10 g/day, < 10 g/day), administration duration (≥ 1 week, < 1 week), exercise type (aerobic, anaerobic), and training status (trained, untrained). The intervention situation showed a significant reduction in indirect markers of EIMD compared to the placebo situation (p = 0.001; I2 = 81%). Subgroup analyses indicated that BCAA administration had a significant reducing effect on creatine kinase levels in trials with a dosage of ≥ 10 g/day, anaerobic exercise, trained individuals, and an ingestion duration of less than 1 week. The findings of this study suggest that BCAA administration reduces EIMD markers following chronic EE in both trained and untrained individuals. BCAA administration reduces creatine kinase activity at 48 hours, 72 hours, and overall post-EE compared to a placebo.