BackgroundThe global shortage of mental health workers has prompted the utilization of technological advancements, such as chatbots, to meet the needs of people with mental health conditions. Chatbots are systems that are able to converse and interact with human users using spoken, written, and visual language. While numerous studies have assessed the effectiveness and safety of using chatbots in mental health, no reviews have pooled the results of those studies. ObjectiveThis study aimed to assess the effectiveness and safety of using chatbots to improve mental health through summarizing and pooling the results of previous studies. MethodsA systematic review was carried out to achieve this objective. The search sources were 7 bibliographic databases (eg, MEDLINE, EMBASE, PsycINFO), the search engine “Google Scholar,” and backward and forward reference list checking of the included studies and relevant reviews. Two reviewers independently selected the studies, extracted data from the included studies, and assessed the risk of bias. Data extracted from studies were synthesized using narrative and statistical methods, as appropriate. ResultsOf 1048 citations retrieved, we identified 12 studies examining the effect of using chatbots on 8 outcomes. Weak evidence demonstrated that chatbots were effective in improving depression, distress, stress, and acrophobia. In contrast, according to similar evidence, there was no statistically significant effect of using chatbots on subjective psychological wellbeing. Results were conflicting regarding the effect of chatbots on the severity of anxiety and positive and negative affect. Only two studies assessed the safety of chatbots and concluded that they are safe in mental health, as no adverse events or harms were reported. ConclusionsChatbots have the potential to improve mental health. However, the evidence in this review was not sufficient to definitely conclude this due to lack of evidence that their effect is clinically important, a lack of studies assessing each outcome, high risk of bias in those studies, and conflicting results for some outcomes. Further studies are required to draw solid conclusions about the effectiveness and safety of chatbots. Trial RegistrationPROSPERO International Prospective Register of Systematic Reviews CRD42019141219; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019141219