Trust underpins much of social and economic exchanges across human societies. In experimental economics, the Trust Game has served as the workhorse for the study of trust in a controlled incentivized setting. Recent evidence using intranasal drug administration, aka ‘sniffing’, suggests that oxytocin (OT) can function as a social hormone facilitating trust and other affiliative behaviors. Here we hypothesized that baseline plasma OT is a biomarker that partially predicts the degree of trust and trustworthiness observed in the trust game. Using a large sample of 1,158 participants, we observed a significant U-shaped relationship between plasma OT with the level of trust, and marginally with the level of trustworthiness, especially among males. Specifically, subjects with more extreme levels of plasma OT were more likely to be trusting as well as trustworthy than those with moderate levels of plasma OT. Our results contribute to a deeper understanding of the biological basis of human trust and underscore the usefulness of peripheral plasma OT measures in characterizing human social behavior.