Background and Aim: Children with Developmental Coordination Disorder (DCD) face significant functional challenges and pronounced motor deficits affecting their daily, academic, and social activities. This situation underscores the critical need for identifying and implementing effective therapeutic interventions. Consequently, this study aimed to examine the effect of a selected games protocol on the level of Brain-Derived Neurotrophic Factor (BDNF) and the development of gross motor skills in children diagnosed with DCD. Methods: This applied study utilized a quasi-experimental, pretest-posttest design with a control group. Forty boys diagnosed with DCD (as confirmed by the Wilson Test) were randomly assigned to either an experimental or a control group. The experimental group participated in the selected games protocol, comprising 24 sessions (8 weeks), while the control group received no intervention. Gross motor skills were assessed using the Gross Motor Development Test – Second Edition, and BDNF levels were measured via serum samples collected at both pre-test and post-test stages. Data were analyzed using Analysis of Covariance (ANCOVA) at a significance level of p<0.05. Results: The findings revealed a statistically significant difference between the experimental and control groups with respect to improvements in both BDNF levels and gross motor skill scores (including running, hopping, leaping, sliding, long jump, and galloping) (p<0.05). In the experimental group, the mean BDNF level and the mean scores of the motor subscales increased substantially. Conclusion: In conclusion, the implementation of selected games as a structured motor intervention can effectively augment BDNF levels and foster substantial development in the gross motor skills of children with DCD. Thus, integrating these types of complex motor interventions into the therapeutic and rehabilitation programs for this population is highly recommended.