The aim of this study was to conduct a comprehensive review on hyperscanning research (measuring brain activity simultaneously from more than two people interacting) using an explicit systematic method, the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Data were searched from IEEE Xplore, PubMed, Engineering Village, Web of Science and Scopus databases. Inclusion criteria were journal articles written in English from 2000 to 19 June 2019. A total of 126 empirical studies were screened out to address three specific questions regarding the neuroimaging method, the application domain, and the experiment paradigm. Results showed that the most used neuroimaging method with hyperscanning was magnetoencephalography/electroencephalography (MEG/EEG; 47%), and the least used neuroimaging method was hyper-transcranial Alternating Current Stimulation (tACS) (1%). Applications in cognition accounted for almost half the studies (48%), while educational applications accounted for less than 5% of the studies. Applications in decision-making tasks were the second most common (26%), shortly followed by applications in motor synchronization (23%). The findings from this systematic review that were based on documented, transparent and reproducible searches should help build cumulative knowledge and guide future research regarding inter-brain neural synchrony during social interactions, that is, hyperscanning research.