Approximately half of all autism spectrum disorder (ASD) individuals suffer from comorbid intellectual disabilities. Furthermore, the prevalence of epilepsy has been estimated to be 46% of patients with low intelligence quotient. It is important to investigate the therapeutic benefits and adverse effects of any recently developed drugs for this proportion of individuals with the so-called Kanner type of ASD. Therefore, we investigated the therapeutic and/or adverse effects of intranasal oxytocin (OT) administration, especially in adolescents and adults with ASD and comorbid intellectual disability and epilepsy, with regard to core symptoms of social deficits. We have already reported three randomized placebo-controlled trials (RCTs). However, we revisit results in our pilot studies from the view of comorbidity. Most of the intellectually disabled participants were found to be feasible participants of the RCT. We observed significantly more events regarded as reciprocal social interaction in the OT group compared with the placebo group. In the trial, no or little differences in adverse events were found between the OT and placebo arms, as found in some other reports. However, seizures were induced in three participants with medical history of epilepsy during or after OT treatment. In conclusion, we stress that behavioral changes in ASD patients with intellectual disabilities could be recognized not by the conventional measurements of ASD symptoms but by detailed evaluation of social interactions arising in daily-life situations.