Background: Attention-deficit/hyperactivity disorder (ADHD) is characterized by behavioral and neurodevelopmental problems. It is estimated that 3 - 7% of children and adolescents suffer from this problem. Apart from synthetic drugs, other effective types of medication like herbal medicines are of great importance. Objectives: This study aimed to evaluate the effectiveness of methylphenidate (MPH) and its combination with Crocus sativus (saffron) in the treatment of children suffering from ADHD. Methods: The sample included 70 children aged between 6 and 16 years who had been diagnosed with ADHD. The patients were randomly assigned into two equal groups (n = 35 in each group). While both groups received 20 or 30 mg/d of MPH (20 and 30 mg/d for < 30 and > 30, respectively), one of them also received 20 or 30 mg/d of saffron in a capsule based on BMI (20 and 30 mg/d for < 30 and > 30, respectively). To collect data, parents and teachers completed Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV). Also, for analyzing the data, the repeated measures analysis of variance (RMANOVA) was used. Results: The results of general linear model (GLM) repeated measures indicated that in both groups, the patients had less symptoms after eight weeks of treatment. However, after four weeks, the average score assigned by the parents and teachers in the MPH with saffron group was lower than the average total score in the MPH group (P < 0.05). Conclusions: Using MPH combined with saffron proved to be more effective in the treatment of patients suffering from ADHD compared to separate treatments. It seems that the duration of therapy can be reduced and the effectiveness be improved by prescribing proposed combined treatment.