This study aimed to evaluate the effects of the goal attainment theory-based nurse-led intervention programs using a systematic review and meta-analysis. Randomized and non-randomized controlled trials, published from January 2001 to December 2020, were examined using four international databases and four domestic databases. The search, selection, and coding were performed independently by two researchers. R version 4.0.3 and Review Manager (version 5.3) were employed for meta-analysis and quality assessment, respectively. Of the 7529 articles retrieved, 18 were selected for analysis. The random overall effect size of the programs was 0.77 (95% CI = 0.61–0.94). Effect size by dependent variables were 2.36 (95% CI = 0.91–3.82), 1.25 (95% CI = 0.66–1.83), 0.83 (95% CI = 0.55–1.10), 0.64 (95% CI = 0.39–0.89), and 0.58 (95% CI = 0.30–0.85) for interpersonal, cognitive, health behavior, psychological, and indicators of physical health, respectively. Effect size by independent variables were 1.25 (95% CI = 0.86–1.64), 0.76 (95% CI = 0.48–1.03), 0.72 (95% CI = 0.37–1.06), 0.35 (95% CI = 0.21–0.49), and 1.35 (95% CI = −0.15–2.85) for prevention, health promotion, counseling and education, goal-setting and health contract, and parent participation programs, respectively. The effect size by control variables was 1.72 (95% CI = 0.88–2.56) at age ≤17, 0.85 (95% CI = 0.54–1.15) at time (min) 61–90, 1.04 (95% CI = 0.76–1.32) at sessions seven to eight, and 0.93 (95% CI = 0.66–1.19) at duration (weeks) five to eight. Thus, these programs were effective in improving various health aspects. Additionally, they can be recommended in various settings. Because efficacy is also influenced by control variables, considering treatment designs based on intervention characteristics and methodological approaches is warranted.