The aim of this study is to analyze the effects of a physical activity program structured as a sports game on social interaction and communication of adolescents with autism spectrum disorder (Asd), in particular Asperger Syndrome (AS). The results of the quantitative survey showed a general improvement in social skills, in particular relating to social interaction and communication, in the experimental group in interim and post-intervention tests. These results were confirmed by the qualitative survey where, based on the parents' perceptions, the interactive skills related to the acceptance of the others, eye contact, cooperative play, involvement and interaction, and social skills related to both receptive communication (attention and understanding) and expressive communication (prompt response, self-expression), had increased. On the contrary, no statistically significant difference was found in the control group. The study concluded that the special structured physical activity program positively influenced the social interaction and communication skills of adolescents with Asd.