This systematic review is to evaluate the effectiveness and cost-effectiveness of mental health interventions delivered by frontline health care workers in disasters and public health emergencies. Six databases and trial registries were searched, and manual searches were conducted. Of the 221 studies identified, 21 were included. Meta-analyses assessed differences between the intervention and control in terms of PTSD outcomes. Eleven studies of 1802 participants were incorporated in the meta-analysis. Interventions delivered or prompted by specialist health care workers showed significant and large effects in improving PTSD-related symptoms with a SMD = 0.99 (95% CI: 0.42-1.57, p = 0.0007). Interventions delivered or prompted by frontline non-specialist health care workers showed significant but small effects in improving PTSD-related symptoms with SMD of 0.25 (95% CI: 0.11-0.39; p = 0.0007). The results showed that most mental health interventions delivered by frontline health care workers effectively supported affected people. Mental health interventions delivered by mental health care professionals are effective in reducing PTSD-related disorders in natural disasters. Future adequately powered RCTs are needed to evaluate the effectiveness of mental health interventions delivered by trained non-specialists. Economic modelling may be useful to estimate cost effectiveness in low- and middle-income countries given the difficulties of conducting studies in disaster and emergency settings.