Temperament, such as behavioral inhibition (BI), has been found to be a predictor of social anxiety in adolescents. Additionally, poor emotional regulation underlies social anxiety. However, it is thought that positive peer friendships may serve as a protective mechanism against social anxiety in BI adolescents. Additionally, prior studies have found that both poor baseline respiratory sinus arrhythmia (RSA) and RSA withdrawal is associated with social anxiety. The goal of the present study is to analyze how peer experiences moderate the association between behavioral inhibition and adolescent social anxiety, and how adolescent social anxiety is associated with biological reactivity to stress during the adolescent developmental period. Results suggest that higher levels of perceived support from a best friend are positively associated with social anxiety specifically for BI adolescents. In addition, lower baseline RSA was associated with higher levels of social anxiety, while RSA reactivity to a stress task was not significantly associated with social anxiety. Overall, our results highlight that BI adolescents’ quality of peer relationships may not necessarily be a protective factor in the development of social anxiety during adolescence. Additionally, adolescents with low baseline RSA may have difficulty regulating emotions, leading to the emergence of social anxiety.