The stigmatization of mental health is present in general hospital settings impacting quality of care. We hypothesized that health professionals in these areas would elicit negative attitudes and a perceived level of dangerousness across a range of mental health disorders. We aimed to conduct a systematic review and meta-analysis to examine these attitudes and perceptions. We searched the bibliographic databases of CINAHL Complete, MEDLINE Complete, PsycINFO, and Psychology and Behavioral Sciences Collection in May 2017 (no date parameters were set). Quantitative studies investigating generalist health professionals’ attitudes towards mental health conditions were selected. Initially, prevalence meta-analyses were conducted to assess the extent of perceived danger, followed by a series of comparative meta-analyses in which the perceived dangerousness of mental health conditions was compared. Of the 653 citations retrieved, eight studies met the inclusion criteria. The overall sample included 2548 health professionals. A majority of health professionals perceived patients with substance use disorder as dangerous 0.60 (95% CI: 0.32–0.88) when compared with patients who had an alcohol-related disorder, schizophrenia, and depression. The results also indicated that a large proportion of staff perceived patients with a diagnosis of schizophrenia as dangerous 0.42 (95% CI: 0.33–0.52). Negative attitudes towards people experiencing mental illness in general hospital settings may be attributed to poor mental health literacy, skills and limited exposure, and social and cultural beliefs about mental illness. Ongoing professional development targeting mental health knowledge is recommended for health professionals working in general hospital settings.