The global COVID-19 pandemic has exerted a profound and lasting impact on adolescent mental health, manifested as a significant increase in symptoms of anxiety, depression, and post-traumatic stress disorder (PTSD). As a non-pharmacological and non-verbal psychological intervention, art therapy demonstrates unique advantages in alleviating psychological distress among adolescents. This study conducted a 12-week randomized controlled trial (RCT) involving 420 adolescents aged 12-18 years to explore the intervention effects of art therapy on mental health outcomes in post-pandemic adolescents and analyze its mechanisms from neurobiological, psychological, and sociological dimensions. The results showed that the art therapy intervention group performed significantly better than the control group in indicators of depression (t=5.78, p<0.001), anxiety (t=6.23, p<0.001), and PTSD (t=4.92, p<0.001), with effect sizes (Cohen's d) for depression, anxiety, and PTSD being 0.89, 0.95, and 0.76, respectively. Mechanism analysis indicated that art therapy exerts its effects by regulating brain neuroplasticity, promoting emotional expression and cognitive restructuring, and enhancing social support networks. This study provides scientific evidence and practical references for interventions targeting mental health outcomes in post-pandemic adolescents.