Pulsed electromagnetic fields (PEMF) delivered by whole-body mats are promoted in many countries for a wide range of therapeutic applications and for enhanced well-being. However, neither the therapeutic efficacy nor the potential health hazards caused by these mats have been systematically evaluated. We conducted a systematic review of trials investigating the therapeutic effects of low-frequency PEMF devices. We were interested in all health outcomes addressed so far in randomized, sham-controlled, double-blind trials. In total, 11 trials were identified. They were focused on osteoarthritis of the knee (3 trials) or the cervical spine (1), fibromyalgia (1), pain perception (2), skin ulcer healing (1), multiple sclerosis-related fatigue (2), or heart rate variability and well-being (1). The sample sizes of the trials ranged from 12 to 71 individuals. The observation period lasted 12 weeks at maximum, and the applied magnetic flux densities ranged from 3.4 to 200 µT. In some trials sporadic positive effects on health were observed. However, independent confirmation of such singular findings was lacking. We conclude that the scientific evidence for therapeutic effects of whole-body PEMF devices is insufficient. Acute adverse effects have not been reported. However, adverse effects occurring after long-term application have not been studied so far. In summary, the therapeutic use of low-frequency whole-body PEMF devices cannot be recommended without more scientific evidence from high-quality, double-blind trials.