Aggression is an important behaviour that concerns individual survival and large-scale social stability. It comprises a variety of psychological subcomponents and is modulated by different biological factors. Two factors in particular, gender and oxytocin, appear to play a robust role in aggressive behaviour. However, whether these two factors interact to impact aggressive behaviour is not currently known. The current study investigated the modulating effect of gender on the relationship between oxytocin and aggression and characterized its underlying mechanisms by combining behavioural economic, pharmacological, and computational approaches. Specifically, we employed a double-blind, randomized, placebo-controlled, between-subjects design, in which one hundred participants (50 men and 50 women) completed a norm-training version of the multi-round one-shot ultimatum game (UG) after intranasal oxytocin or placebo administration. Rejection rates in the UG were adopted as an indicator of reactive aggression. The results indicated that oxytocin compared with placebo administration decreased aggression among men but not among women. Further analyses suggested that this decrease in aggression was a result of changes in men’s sensitivity to provocation and positive affect, rather than norm adaptation rates or concerns about the cost of aggression. These findings highlight the role of gender in the relationship between oxytocin and reactive aggression and reveal its underlying psychological and computational mechanisms.