This systematic review examines the synergistic effects of Cycloserine and anodal transcranial direct current stimulation (tDCS) on cortical excitability and clinical outcomes. tDCS, a non-invasive neuromodulation technique, modulates cortical excitability, potentially enhancing neuroplasticity. Cycloserine, a partial agonist at NMDA receptors, may potentiate tDCS effects by stabilizing receptor activity. A comprehensive database search identified five eligible studies focusing on healthy participants, with one involving patients with depression. Meta-analysis revealed that Cycloserine prolonged cortical excitability 60 min post-tDCS (SMD: 0.66, 95% CI: 0.05 to 1.27), with the greatest effect observed at a 100 mg dosage (SMD: 0.78, 95% CI: 0.26 to 1.31). Although this suggests a potential enhancement of tDCS efficacy, clinical improvements, such as in depression or motor learning, were not consistently significant across studies. Overall, while Cycloserine appears to extend tDCS-induced cortical excitability, more robust clinical trials are necessary to confirm its therapeutic benefits.