With first indications of resistance against artemisinin compounds, the development of novel alternative antimalarials remains an urgent need. One candidate is fosmidomycin (Fos), a phosphonic acid derivative. This PRISMA guideline-adhering and PROSPERO-registered systematic review and meta-analysis provides an overview of the state-of-the-art of the clinical development of Fos as an antimalarial. Pooling six clinical trials of Fos against uncomplicated malaria in African children yielded an overall day 28 cure rate of 85% (95% CI: 71-98%); a parasite clearance time of 39 h; and a fever clearance time of 30 h. In four adult cohorts, the corresponding values were 70% (95% CI: 40-100%), 49 and 42 h, respectively. Data suggest that besides the partner drug, formulation determines efficacy. We advocate further clinical development of Fos-combinations. PROSPERO registration number: CRD42014013688.