Attention-deficit/hyperactivity disorder (ADHD) is a neurobiological disorder. Common symptoms are inattention, hyperactivity, impulsivity, and executive functions deficit, often with comorbidities. Main treatment involves pharmacological and non-pharmacological therapies (cognitive-behavioral therapy, psycho-pedagogical programs). Emerging non-pharmacological treatments include manual therapies (MTs) in mental health. Several MT techniques have shown effectiveness in ADHD. The objectives of this study are as follows: (1) to assess short-term effects and persistence of an MT program on neuropsychological (hyperactivity index through the Conners' Global Index [CGI]) and neurophysiological (time-frequency domain parameters of heart rate variability [HRV]) variables in ADHD children; and (2) to test the feasibility of the design. This study was approved by the Parc Tauli Corporation Clinical Research Ethics Board (#2017311). Pilot, controlled, multidisciplinary study of eight children with ADHD randomly assigned to control group (CG; n = 4) and intervention group (IG; n = 4). Both followed multimodal treatment, and IG also received an MT program per week for 4 weeks. A physiotherapist and a psychologist analyzed short-term effects (1-week post-program) and persistence (36 weeks). Eight children (boys, 62.5%; girls, 37.5%) with an average age of 10.375 ± 0.74 years were included. Baseline HRV parameters showed basal sympathetic predominance. The MT program increased the parasympathetic activity, which was significantly maintained at 1 to 36 weeks; there were no changes in CG. One-week post-program IG showed significant CGI reduction (-7 points, p = 0.016*), CG without changes (p = 0.41), with significant differences CG - IG (p = 0.0097*), and very large effect size (d = 2.235); 36 weeks post-program showed no effects (IG, p = 0.293; CG, p = 0.247), without differences CG - IG (p = 0.369). The MT program reduced the hyperactivity index with a 1-week persistence and increased the parasympathetic activity with a 36-week persistence. More investigations are needed to generalize the outcomes. Additional research is planned to further explore the possibilities of MT in psychiatric disorders with autonomic imbalances.