Technological advancement is constantly evolving, and it is also developing in the mental health field. Various applications, often based on virtual reality, have been implemented to carry out psychological assessments and interventions, using innovative human–machine interaction systems. In this context, the LEAP Motion sensing technology has raised interest, since it allows for more natural interactions with digital contents, via an optical tracking of hand and finger movements. Recent research has considered LEAP Motion features in virtual-reality-based systems, to meet specific needs of different clinical populations, varying in age and type of disorder. The present paper carried out a systematic mini-review of the available literature using Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The inclusion criteria were (i) publication date between 2013 and 2020, (ii) being an empirical study or project report, (iii) written in English or Italian languages, (iv) published in a scholarly peer-reviewed journal and/or conference proceedings, and (v) assessing LEAP Motion intervention for four specific psychological domains (i.e., autism spectrum disorder, attention-deficit/hyperactivity disorder, dementia, and mild cognitive impairment), objectively. Nineteen eligible empirical studies were included. Overall, results show that protocols for attention-deficit hyperactivity disorder and autism spectrum disorder can promote psychomotor and psychosocial rehabilitation in contexts that stimulate learning. Moreover, virtual reality and LEAP Motion seem promising for the assessment and screening of functional abilities in dementia and mild cognitive impairment. As evidence is, however, still limited, deeper investigations are needed to assess the full potential of the LEAP Motion technology, possibly extending its applications. This is relevant, considering the role that virtual reality could have in overcoming barriers to access assessment, therapies, and smart monitoring.