Background: Callous-unemotional traits (CUT) are an antisocial personality trait, which can be present in people with autism spectrum disorder (ASD), especially in relation to difficulties in empathy. These traits are related to challenging behaviors, such as aggressive behavior, which may occur in people with ASD. Method: This study aimed to expand the understanding of the role of CUT in adults with ASD and intellectual disability (ID). Eighty-three adults with a diagnosis of ASD and ID participated in the study. Results: Mediation analyses found that CUT indirectly mediated the relationship between ASD symptomatology and the frequency of self-injuries and stereotypies, but not aggression. Conclusions: It is considered that CUT may have a protective effect on the presence of individual challenging behaviors in adults with ASD and ID. The apparent relationship between CUT and executive functioning was discussed. CUT traits may be considered as a variable to contemplate in relation to interventions in challenging behaviors in the ASD population, especially in those individuals who show aggression-related behaviors and who have a higher executive level.