BackgroundChronic and mental health conditions are increasingly prevalent worldwide. As devices in our everyday lives offer more and more voice-based self-service, voice-based conversational agents (VCAs) have the potential to support the prevention and management of these conditions in a scalable manner. However, evidence on VCAs dedicated to the prevention and management of chronic and mental health conditions is unclear.ObjectiveThis study provides a better understanding of the current methods used in the evaluation of health interventions for the prevention and management of chronic and mental health conditions delivered through VCAs.MethodsWe conducted a systematic literature review using PubMed MEDLINE, Embase, PsycINFO, Scopus, and Web of Science databases. We included primary research involving the prevention or management of chronic or mental health conditions through a VCA and reporting an empirical evaluation of the system either in terms of system accuracy, technology acceptance, or both. A total of 2 independent reviewers conducted the screening and data extraction, and agreement between them was measured using Cohen kappa. A narrative approach was used to synthesize the selected records.ResultsOf 7170 prescreened papers, 12 met the inclusion criteria. All studies were nonexperimental. The VCAs provided behavioral support (n=5), health monitoring services (n=3), or both (n=4). The interventions were delivered via smartphones (n=5), tablets (n=2), or smart speakers (n=3). In 2 cases, no device was specified. A total of 3 VCAs targeted cancer, whereas 2 VCAs targeted diabetes and heart failure. The other VCAs targeted hearing impairment, asthma, Parkinson disease, dementia, autism, intellectual disability, and depression. The majority of the studies (n=7) assessed technology acceptance, but only few studies (n=3) used validated instruments. Half of the studies (n=6) reported either performance measures on speech recognition or on the ability of VCAs to respond to health-related queries. Only a minority of the studies (n=2) reported behavioral measures or a measure of attitudes toward intervention-targeted health behavior. Moreover, only a minority of studies (n=4) reported controlling for participants’ previous experience with technology. Finally, risk bias varied markedly.ConclusionsThe heterogeneity in the methods, the limited number of studies identified, and the high risk of bias show that research on VCAs for chronic and mental health conditions is still in its infancy. Although the results of system accuracy and technology acceptance are encouraging, there is still a need to establish more conclusive evidence on the efficacy of VCAs for the prevention and management of chronic and mental health conditions, both in absolute terms and in comparison with standard health care.